sincalide and Body-Weight

sincalide has been researched along with Body-Weight* in 85 studies

Trials

2 trial(s) available for sincalide and Body-Weight

ArticleYear
Variation in exocrine pancreatic secretion in rats due to different commercial diets.
    Lab animal, 2006, Volume: 35, Issue:6

    The diet fed to laboratory animals is one of many variables that can confound research results. The authors investigated the effect of the composition of commercial standard rodent diets on exocrine pancreatic function in rats. They compared two widely used commercial animal diets and found that diet composition greatly influences pancreatic secretion. Their results indicate that commercial diets should conform to the recommended composition requirements to avoid alterations in physiological functions that would eventually affect the results of biomedical research and that investigators should be keenly aware of the composition of the diets being fed to their animals.

    Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Male; Pancreas; Pancreatic Juice; Rats; Rats, Sprague-Dawley; Secretin; Sincalide

2006
C-terminal octapeptide of cholecystokinin decreases food intake in obese men.
    Physiology & behavior, 1982, Volume: 29, Issue:4

    Six of eight obese men ate significantly less food during an intravenous infusion of the C-terminal octapeptide of cholecystokinin (CCK-8, 4 ng . kg-1 . min-1) than during a saline infusion in a double blind experimental paradigm. Subjects stopped eating sooner during CCK-8. CCK-8 did not change the rate of eating. No overt side effects were reported or observed. This is the first report of the satiety effect of CCK-8 in obese humans and it suggests that the therapeutic potential of CCK-8 for the treatment of obesity deserves investigation.

    Topics: Body Weight; Cholecystokinin; Eating; Energy Intake; Humans; Male; Obesity; Peptide Fragments; Sincalide

1982

Other Studies

83 other study(ies) available for sincalide and Body-Weight

ArticleYear
Leonurine hydrochloride-a new drug for the treatment of menopausal syndrome: Synthesis, estrogen-like effects and pharmacokinetics.
    Fitoterapia, 2022, Volume: 157

    This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through

    Topics: Animals; Biological Availability; Blotting, Western; Body Weight; Estrus; Female; Gallic Acid; Humans; Hydroxybenzoates; Male; Menopause; Mice; Mice, Inbred ICR; Ovary; Random Allocation; Rats; Sincalide; Uterus; Vagina

2022
Infusion of exogenous cholecystokinin-8, gastrin releasing peptide-29 and their combination reduce body weight in diet-induced obese male rats.
    Appetite, 2017, 02-01, Volume: 109

    We hypothesized that exogenous gastrin releasing peptide-29 (GRP-29), cholecystokinin-8 (CCK-8) and their combination reduce body weight (BW). To test this hypothesis, BW was measured in four groups of diet-induced obese (DIO) male rats infused in the aorta (close to the junctions of the celiac and cranial mesenteric arteries) with saline, CCK-8 (0.5 nmol/kg), GRP-29 (0.5 nmol/kg) and CCK-8+GRP-29 (0.5 nmol/kg each) once daily for a total of 23 days. We found that CCK-8, GRP-29 and CCK-8+GRP-29 reduce BW relative to saline control. In conclusion, CCK-8, GRP-29 and their combination reduce BW in the DIO rat model. If infused near their gastrointestinal sites of action CCK-8, GRP-29 and their combination may have a role in regulating BW.

    Topics: Animals; Body Weight; Cholecystokinin; Diet; Drug Therapy, Combination; Gastrin-Releasing Peptide; Gastrointestinal Agents; Infusions, Parenteral; Male; Obesity; Peptide Fragments; Rats; Weight Loss

2017
Studies on the influence of CCK-8 on the ability of obestatin to reduce food intake, gain in body weight and related lipid parameters.
    Biochimie, 2016, Volume: 125

    In an effort to mimic in part the redundancy of satiety peptides involved in energy homeostasis, the combined benefits of the well-established satiety peptide CCK8 and an apparently anorectic peptide obestatin were studied in Swiss albino mice. The optimal dose of obestatin that was required to give the most pronounced effect with CCK8 was worked out by varying the concentration of obestatin while keeping CCK8 concentration constant at 200 nmol/KgBW. Mice administered 160 nmol obestatin and 200 nmol CCK8 per kilogram body weight showed the most drastic reduction in food intake. Gain in body weight was arrested after day four during the eight day experiment. These studies reemphasize the beneficial effects imparted by co-administration of obestatin and CCK8 and their potential use towards countering obesity.

    Topics: Animals; Body Weight; Eating; Lipid Metabolism; Male; Mice; Obesity; Peptide Hormones; Sincalide

2016
Astilbin ameliorates experimental autoimmune myasthenia gravis by decreased Th17 cytokines and up-regulated T regulatory cells.
    Journal of neuroimmunology, 2016, 09-15, Volume: 298

    Astilbin, a major bioactive compound extracted from Rhizoma smilacis glabrae (RSG), has been reported to possess immunosuppressive properties. Our study first evaluated the effect of astilbin on experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. The results showed that astilbin could attenuate the severity of EAMG by decreasing antigen-specific autoantibodies with up-regulation of regulatory T cells and down-regulation of Th17 cells. In addition to, astilbin also reduced the efficiency of the antigen presenting cells on which the expression of MHC class II decreased. These results suggest that astilbin might be a candidate drug for immunoregulation of EAMG, and provide us new treatment ideas for human myasthenia gravis (MG).

    Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Antigens, CD; Body Weight; Cell Proliferation; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Flavonols; Flow Cytometry; HLA-DR alpha-Chains; Myasthenia Gravis, Autoimmune, Experimental; Rats; Rats, Inbred Lew; Sincalide; T-Lymphocytes, Regulatory; Th17 Cells

2016
Chemical cholecystokinin receptor activation protects against obesity-diabetes in high fat fed mice and has sustainable beneficial effects in genetic ob/ob mice.
    Biochemical pharmacology, 2013, Jan-01, Volume: 85, Issue:1

    The current study has determined the ability of (pGlu-Gln)-CCK-8 to counter the development of diet-induced obesity-diabetes and examined persistence of beneficial metabolic effects in high fat and ob/ob mice, respectively. Twice daily injection of (pGlu-Gln)-CCK-8 in normal mice transferred to a high fat diet reduced energy intake (p < 0.001), body weight (p < 0.01), circulating insulin and LDL-cholesterol (p < 0.001) and improved insulin sensitivity (p < 0.001) as well as oral and intraperitoneal (p < 0.001) glucose tolerance. Energy intake, body weight, circulating insulin and glucose tolerance of (pGlu-Gln)-CCK-8 mice were similar to lean controls. In addition, (pGlu-Gln)-CCK-8 prevented the effect of high fat feeding on triacylglycerol accumulation in liver and muscle. Interestingly, (pGlu-Gln)-CCK-8 significantly (p < 0.001) elevated pancreatic glucagon content. Histological examination of the pancreata of (pGlu-Gln)-CCK-8 mice revealed no changes in islet number or size, but there was increased turnover of beta-cells with significantly (p < 0.001) increased numbers of peripherally located alpha-cells, co-expressing both glucagon and GLP-1. Beneficial metabolic effects were observed similarly in ob/ob mice treated twice daily with (pGlu-Gln)-CCK-8 for 18 days, including significantly reduced energy intake (p < 0.05), body weight (p < 0.05 to p < 0.01), circulating glucose (p < 0.05 to p < 0.01) and insulin (p < 0.05 to p < 0.001) and improved glucose tolerance (p < 0.05) and insulin sensitivity (p < 0.001). Notably, these beneficial effects were still evident 18 days following cessation of treatment. These studies emphasize the potential of (pGlu-Gln)-CCK-8 for the treatment of obesity-diabetes.

    Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Dietary Fats; Eating; Glucagon; Glucose Tolerance Test; Insulin; Insulin Resistance; Lipids; Mice; Mice, Obese; Obesity; Pancreas; Receptors, Cholecystokinin; Sincalide

2013
Comparison of the independent and combined metabolic effects of subchronic modulation of CCK and GIP receptor action in obesity-related diabetes.
    International journal of obesity (2005), 2013, Volume: 37, Issue:8

    Compromise of gastric inhibitory polypeptide (GIP) receptor action and activation of cholecystokinin (CCK) receptors represent mechanistically different approaches to the possible treatment of obesity-related diabetes. In the present study, we have compared the individual and combined effects of (Pro(3))GIP[mPEG] and (pGlu-Gln)-CCK-8 as an enzymatically stable GIP receptor antagonist and CCK receptor agonist molecule, respectively.. Twice-daily injections of (pGlu-Gln)-CCK-8 alone and in combination with (Pro(3))GIP[mPEG] in high-fat-fed mice for 34 days significantly decreased the energy intake throughout the entire study (P<0.05 to P<0.01). Body weights were significantly depressed (P<0.05 to P<0.01) in all treatment groups from day 18 onwards. Administration of (pGlu-Gln)-CCK-8, (Pro(3))GIP[mPEG] or a combination of both peptides significantly (P<0.01 to P<0.001) decreased the overall glycaemic excursion in response to both oral and intraperitoneal glucose challenge when compared with the controls. Furthermore, oral glucose tolerance returned to lean control levels in all treatment groups. The beneficial effects on glucose homeostasis were not associated with altered insulin levels in any of the treatment groups. In keeping with this, the estimated insulin sensitivity was restored to control levels by twice-daily treatment with (pGlu-Gln)-CCK-8, (Pro(3))GIP[mPEG] or a combination of both peptides. The blood lipid profile on day 34 was not significantly different between the high-fat controls and all treated mice.. These studies highlight the potential of (pGlu-Gln)-CCK-8 and (Pro(3))GIP[mPEG] in the treatment of obesity-related diabetes, but there was no evidence of a synergistic effect of the combined treatment.

    Topics: Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Drug Therapy, Combination; Energy Intake; Insulin Resistance; Male; Mice; Obesity; Receptors, Cholecystokinin; Receptors, Gastrointestinal Hormone; Sincalide; Time Factors

2013
Ileal interposition attenuates the satiety responses evoked by cholecystokinin-8 and -33.
    Peptides, 2011, Volume: 32, Issue:6

    One of the possible mechanisms by which the weight-reducing surgical procedure ileal interposition (II) works is by increasing circulating levels of lower gut peptides that reduce food intake, such as glucagon like peptide-1 and peptide YY. However, since this surgery involves both lower and upper gut segments, we tested the hypothesis that II alters the satiety responses evoked by the classic upper gut peptide cholecystokinin (CCK). To test this hypothesis, we determined meal size (MS), intermeal interval (IMI) and satiety ratio (SR) evoked by CCK-8 and -33 (0, 1, 3, 5nmol/kg, i.p.) in two groups of rats, II and sham-operated. CCK-8 and -33 reduced MS more in the sham group than in the II group; CCK-33 prolonged IMI in the sham group and increased SR in both groups. Reduction of cumulative food intake by CCK-8 in II rats was blocked by devazepide, a CCK(1) receptor antagonist. In addition, as previously reported, we found that II resulted in a slight reduction in body weight compared to sham-operated rats. Based on these observations, we conclude that ileal interposition attenuates the satiety responses of CCK. Therefore, it is unlikely that this peptide plays a significant role in reduction of body weight by this surgery.

    Topics: Animals; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Ileum; Jejunoileal Bypass; Jejunum; Male; Peptide Fragments; Rats; Rats, Wistar; Receptors, Cholecystokinin; Satiety Response

2011
Effect of feed restriction and supplemental dietary fat on gut peptide and hypothalamic neuropeptide messenger ribonucleic acid concentrations in growing wethers.
    Journal of animal science, 2010, Volume: 88, Issue:2

    The objectives of the present study were 1) to evaluate the effects of supplemental fat and ME intake on plasma concentrations of glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide, ghrelin, and oxyntomodulin; and 2) to determine the association of these peptides with DMI and the hypothalamic concentration of mRNA for the following neuropeptides: neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). In a completely randomized block design with a 2 x 2 factorial arrangement of treatments, 32 pens with 2 wethers each were restricted-fed (2.45 Mcal/lamb per day) or offered diets ad libitum (n = 16) with or without 6% supplemental fat (n = 16) for a period of 30 d. Dry matter intake was measured daily. On d 8, 15, 22, and 29, BW was measured before feeding, and 6 h after feeding, blood samples were collected for plasma measurement of insulin, GLP-1, CCK, ghrelin, glucose-dependent insulinotropic polypeptide, oxyntomodulin, glucose, and NEFA concentrations. On d 29, blood was collected 30 min before feeding for the same hormone and metabolite analyses. At the end of the experiment, wethers were slaughtered and the hypothalami were collected to measure concentrations of NPY, AgRP, and POMC mRNA. Offering feed ad libitum (resulting in greater ME intake) increased plasma insulin and NEFA concentrations (P = 0.02 and 0.02, respectively) and decreased hypothalamic mRNA expression of NPY and AgRP (P = 0.07 and 0.02, respectively) compared with the restricted-fed wethers. There was a trend for the addition of dietary fat to decrease DMI (P = 0.12). Addition of dietary fat decreased insulin and glucose concentrations (P < 0.05 and 0.01, respectively) and tended to increase hypothalamic mRNA concentrations for NPY and AgRP (P = 0.07 and 0.11, respectively). Plasma GLP-1 and CCK concentrations increased in wethers offered feed ad libitum compared with restricted-fed wethers, but the response was greater when wethers were offered feed ad libitum and had supplemental fat in the diet (fat x intake interaction, P = 0.04). The prefeeding plasma ghrelin concentration was greater in restricted-fed wethers compared with those offered feed ad libitum, but the concentrations were similar 6 h after feeding (intake x time interaction, P < 0.01). Supplemental dietary fat did not affect (P = 0.22) plasma ghrelin concentration. We conclude that insulin, ghrelin, CCK, and GLP-1 may regulate DMI in sheep by

    Topics: Animals; Body Weight; Cholecystokinin; Dietary Fats; Eating; Fasting; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Hypothalamus; Male; Oxyntomodulin; Peptide Fragments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sheep

2010
Normal feeding and body weight in Fischer 344 rats lacking the cholecystokinin-1 receptor gene.
    Brain research, 2009, Feb-19, Volume: 1255

    A large body of evidence has demonstrated that one mechanism by which cholecystokinin (CCK) inhibits food intake through activation of CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. OLETF rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic, obese, and predisposed to type 2 diabetes. Recently, by introgressing the OLETF-derived, CCK1R-null gene onto a Fischer 344 genetic background, we have been able to generate a CCK1R-deficient, congenic rat strain, F344.Cck1r(-/-), that in contrast to OLETF rats, possesses a lean and normoglycemic phenotype. In the present study, the behavioral and neurobiological phenotype of this rat strain was characterized more fully. As expected, intraperitoneal injections of CCK-8 inhibited intake of chow and Ensure Plus and induced Fos responses in the area postrema and the gelatinosus, commissural and medial subdivisions of the nucleus tractus solitarius of wild-type F344.Cck1r(+/+) rats, whereas CCK-8 was without effect on food intake or Fos induction in the F344.Cck1r(-/-) rats. F344.Cck1r(-/-) and F344.Cck1r(+/+) rats did not differ in body weight and showed comparable weight gain when maintained on Ensure Plus for 2 weeks. Also, no difference was found in 24-h food intake, and dark-phase meal frequency or meal size between F344.Cck1r(+/+) and F344.Cck1r(-/-) rats. As expected, blockade of endogenous CCK action at CCK1R increased food intake and blocked the effects of peripheral CCK-8 in wild-type F344.Cck1r(+/+) rats. These results confirm that in rats with a F344 background, CCK-1R mediates CCK-8-induced inhibition of food intake and Fos activation in the hindbrain and demonstrate that selective genetic ablation of CCK1R is not associated with altered meal patterns, hyperphagia, or excessive weight gain on a palatable diet.

    Topics: Animals; Body Weight; Cholecystokinin; Eating; Feeding Behavior; Genotype; Immunohistochemistry; Injections, Intraperitoneal; Male; Peptide Fragments; Polymerase Chain Reaction; Proto-Oncogene Proteins c-fos; Rats; Rats, Inbred F344; Rats, Transgenic; Receptor, Cholecystokinin A

2009
Circadian rhythm drives the responsiveness of leptin-mediated hypothalamic pathway of cholecystokinin-8.
    Neuroscience letters, 2008, Sep-12, Volume: 442, Issue:2

    Cholecystokinin (CCK) and leptin act coordinately in the brain to regulate food intake and energy balance. Recently we have reported that CCK enhances the permeability of brain barriers to leptin and we have proposed that CCK enhances energy expenditure in rats by activating in the hypothalamus the janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, which is coupled to leptin receptors. Because plasma leptin concentration follows a circadian rhythm (plasma leptin concentration rise maximal values during the night, after rats start eating), we have hypothesized that the interaction between leptin and CCK should be more intense in animals receiving CCK during the night, i.e., during periods of positive energy balance. In order to further characterize the physiological relevance of the interplay between leptin and CCK we have compared the effect of diurnal vs. nocturnal administration of the C-terminal octapeptide of CCK (CCK-8) on (i) body weight and food intake, and (ii) STAT3 activation, by analyzing phosphorylated STAT3 (pSTAT3) immunostaining within the arcuate nucleus of the hypothalamus. Our results show that CCK decreases body weight and food intake only after p.m. administration. Accordingly pSTAT3 immunostaining within the hypothalamus was more intense in p.m. than in a.m.-treated animals. These data suggest that the effect of CCK on leptin pathways follows a circadian rhythm linked to the energy balance status and gives further support to the interaction between leptin and CCK.

    Topics: Animals; Behavior, Animal; Body Weight; Circadian Rhythm; Dose-Response Relationship, Drug; Eating; Gene Expression Regulation; Hypothalamus; Leptin; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Sincalide; STAT3 Transcription Factor

2008
Leptin-mediated hypothalamic pathway of cholecystokinin (CCK-8) to regulate body weight in free-feeding rats.
    Endocrinology, 2008, Volume: 149, Issue:4

    Regulation of body weight (BW) results from the interplay between different hormonal systems acting at central and peripheral level. This study aims at characterizing the involvement of cholecystokinin (CCK) in BW and energy balance regulation. We have characterized, in free-feeding rats, the effect of CCK-8 on 1) food intake, BW, and adiposity; 2) skeletal muscle metabolism; 3) leptin signaling pathway within the arcuate nucleus of the hypothalamus; and 4) the permeability of brain barriers to leptin. We demonstrate here that CCK-8 acutely decreases BW by a mechanism partially dependent on central leptin pathways, based on the following results: 1) the effect of CCK was less intense in rats lacking functional leptin receptors (Zucker fa/fa), 2) CCK-8 facilitated the uptake of leptin from peripheral circulation to cerebrospinal fluid (CSF), 3) the concentration of leptin in CSF of rats receiving CCK was more elevated in those animals showing higher loss of BW, and 4) CCK activated leptin signaling pathways within the hypothalamus as well as phosphorylation of AMP-activated protein kinase in skeletal muscle. We also suggest that gain of BW may be linked to individual susceptibility to the effect of CCK, because we observed that in animals treated with this hormone, the increase of BW negatively correlated with leptin concentration within the CSF. Our data show that CCK has a negative impact on energy balance and suggest that CCK facilitates the access of leptin to hypothalamic areas, thus allowing leptin to act on hypothalamic targets involved in BW control.

    Topics: Acetyl-CoA Carboxylase; Adipose Tissue; Adiposity; AMP-Activated Protein Kinases; Animals; Body Weight; Eating; Hypothalamus; Leptin; Male; Multienzyme Complexes; Muscle, Skeletal; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Sincalide; STAT3 Transcription Factor

2008
Effects of bee venom on cholecystokinin octapeptide-induced acute pancreatitis in rats.
    Pancreas, 2008, Volume: 36, Issue:2

    Bee venom (BV) has frequently been used as a remedy for inflammatory diseases. The aim of this study was to investigate the effect of BV on cholecystokinin octapeptide (CCK-8)-induced acute pancreatitis (AP) in rats.. The BV pretreatment group: 0.25 mg/kg BV was administered subcutaneously, followed by 75 mug/kg CCK-8 subcutaneously 3 times after 1, 3, and 5 hours. This whole procedure was repeated for 5 days.. CCK-8 subcutaneously 3 times after 1, 3, and 5 hours for 5 days. The BV posttreatment group: CCK-8 subcutaneously 3 times at an interval of 2 hours for 3 days, and then 0.25 mg/kg of BV was administered subcutaneously.. CCK-8 subcutaneously 3 times at an interval of 2 hours for 3 days.. The BV pretreatment and posttreatment ameliorated many of the examined laboratory parameters (the pancreatic weight [PW]/body weight [BW] ratio, the serum amylase and lipase activity) and reduced histological damages in pancreas. Furthermore, BV pretreatment reduced the production of tumor necrosis factor-alpha, interleukin 1, and interleukin 6 and also decreased pancreatic nuclearfactor-kappaB binding activity compared with saline-treated group in the AP model. The BV also increased heat shock protein 60 (HSP60) and heat shock protein 72 (HSP72) compared with the saline-treated group in the AP model.. These findings suggest that the anti-inflammatory effect of BV in CCK-8-induced AP seems to be mediated by inhibiting nuclear factor-kappaB binding activity, and that BV may have a protective effect against AP.

    Topics: Acute Disease; Amylases; Animals; Anti-Inflammatory Agents; Bee Venoms; Body Weight; Chaperonin 60; Disease Models, Animal; HSP72 Heat-Shock Proteins; Injections, Subcutaneous; Interleukin-1; Interleukin-6; Lipase; Male; NF-kappa B; Organ Size; Pancreas; Pancreatitis; Rats; Rats, Wistar; Severity of Illness Index; Sincalide; Tumor Necrosis Factor-alpha

2008
Beneficial effect of resveratrol on cholecystokinin-induced experimental pancreatitis.
    European journal of pharmacology, 2006, Feb-17, Volume: 532, Issue:1-2

    Resveratrol is a phytoalexin with strong antioxidant and anti-inflammatory effects reaching high concentrations in red wine. The aim of our study was to test the effects of resveratrol pretreatment on cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis in rats. Animals were divided into a control group, a group treated with CCK-8 and a group receiving 10 mg/kg resveratrol prior to CCK-8 administration. Resveratrol ameliorated the CCK-8-induced changes in the laboratory parameters, and reduced the histological damage in the pancreas. The drug failed to improve the pancreatic antioxidant state, but increased the amount of hepatic reduced glutathione and prevented the reduction of hepatic catalase activity. Resveratrol-induced inhibition of nuclear factor kappa B (NF-kappaB) activation or reduction of the pancreatic tumor necrosis factor-alpha (TNF-alpha) concentration could not be demonstrated. In conclusion, the beneficial effects of resveratrol on acute pancreatitis seem to be mediated by the antioxidant effect of resveratrol or by an NF-kappaB-independent anti-inflammatory mechanism.

    Topics: Acute Disease; Amylases; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspartate Aminotransferases; Blood Glucose; Blood Urea Nitrogen; Body Weight; Calcium; Catalase; Creatinine; Glutathione; Glutathione Peroxidase; Immunohistochemistry; Injections, Intraperitoneal; Injections, Subcutaneous; Lipase; Liver; Male; NF-kappa B; Nitric Oxide Synthase Type III; Organ Size; Pancreas; Pancreatitis; Rats; Rats, Wistar; Resveratrol; Sincalide; Stilbenes; Superoxide Dismutase; Time Factors; Triglycerides; Tumor Necrosis Factor-alpha

2006
Inhibitory effect of Patrinia scabiosaefolia on acute pancreatitis.
    World journal of gastroenterology, 2006, Feb-21, Volume: 12, Issue:7

    To investigate the effect of Patrinia scabiosaefolia (PS) on the cholecystokinin (CCK) octapeptide-induced acute pancreatitis (AP) in rats.. Wistar rats weighing 240-260 g were divided into three groups: (1) Normal saline-treated group; (2) treatment with PS at 100 mg/kg group, in which PS was administered orally, followed by subcutaneous administration of 75 microg/kg CCK octapeptide three times after 1, 3 and 5 h, and this whole procedure was repeated for 5 d; (3) treatment with saline group, in which the protocols were the same as in treatment group with PS. We determined the pancreatic weight/body weight ratio, the levels of pancreatic HSP60, HSP72 and the secretion of pro-inflammatory cytokines. Repeated CCK octapeptide treatment resulted in the typical laboratory findings of experimentally induced pancreatitis.. PS reduced the pancreatic weight/body weight ratio, the levels of serum amylase and lipase, and inhibited expressions of pro-inflammatory cytokines in the CCK octapeptide-induced AP. Furthermore, PS pretreatment increased the pancreatic levels of HSP60 and HSP72.. Pretreatment with PS has an anti-inflammatory effect on CCK octapeptide-induced AP.

    Topics: Acute Disease; Amylases; Animals; Blotting, Western; Body Weight; Chaperonin 60; Cytokines; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Enzymologic; HSP72 Heat-Shock Proteins; Lipase; Male; Organ Size; Pancreas; Pancreatitis; Patrinia; Phytotherapy; Plant Preparations; Rats; Rats, Wistar; Sincalide

2006
Taraxacum officinale protects against cholecystokinin-induced acute pancreatitis in rats.
    World journal of gastroenterology, 2005, Jan-28, Volume: 11, Issue:4

    Taraxacum officinale (TO) has been frequently used as a remedy for inflammatory diseases. The aim of this study was to investigate the effect of TO on cholecystokinin (CCK)-octapeptide-induced acute pancreatitis in rats.. TO at 10 mg/kg was orally administered, followed by 75 microg/kg CCK octapeptide injected subcutaneously three times after 1, 3 and 5 h. This whole procedure was repeated for 5 d. We determined the pancreatic weight/body weight ratio, the levels of pancreatic HSP60 and HSP72, and the secretion of pro-inflammatory cytokines. Repeated CCK octapeptide treatment resulted in typical laboratory and morphological changes of experimentally-induced pancreatitis.. TO significantly decreased the pancreatic weight/body weight ratio in CCK octapeptide-induced acute pancreatitis. TO also increased the pancreatic levels of HSP60 and HSP72. Additionally, the secretion of IL-6 and TNF-alpha decreased in the animals treated with TO.. TO may have a protective effect against CCK octapeptide-induced acute pancreatitis.

    Topics: Acute Disease; Animals; Body Weight; Chaperonin 60; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Male; Organ Size; Pancreas; Pancreatitis; Phytotherapy; Plant Preparations; Rats; Rats, Wistar; Sincalide; Taraxacum

2005
A nuclear import inhibitory peptide ameliorates the severity of cholecystokinin-induced acute pancreatitis.
    World journal of gastroenterology, 2005, Feb-21, Volume: 11, Issue:7

    To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-kappaB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-kappaB p50 subunit.. Pancreatitis was induced in male Wistar rats by administering 2X100 mug/kg body weight of cholecystokinin-octapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.. All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity, pancreatic levels of TNF-alpha and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-kappaB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide. According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.. Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-kappaB might be clinically useful for the suppression of the severity of acute pancreatitis.

    Topics: Active Transport, Cell Nucleus; Acute Disease; Amino Acid Sequence; Amylases; Animals; Body Weight; Cell Line, Transformed; Electrophoretic Mobility Shift Assay; Glutathione; Interleukin-6; Lipid Peroxidation; Lung; Male; Mice; Molecular Sequence Data; NF-kappa B; Organ Size; Pancreas; Pancreatitis; Peptides; Peroxidase; Rats; Rats, Wistar; Sincalide; Transcription, Genetic; Tumor Necrosis Factor-alpha

2005
Satiety enhancement by selective orexin-1 receptor antagonist SB-334867: influence of test context and profile comparison with CCK-8S.
    Behavioural brain research, 2005, May-07, Volume: 160, Issue:1

    Acute systemic treatment with the selective orexin-1 (OX1R) antagonist SB-334867 reduces food intake in rats, an effect associated with an acceleration in behavioural satiety and unrelated to gross behavioural disruption, alterations in palatability, or toxicity. However, as enhanced satiety is behaviourally indexed by an earlier-than-normal transition from eating to resting, and since orexin-A has been implicated in mechanisms of arousal, it remains possible that sedation contributes to the anorectic effect of acute OX1R blockade. Previous work has shown that, when treated with SB-334867 (30 mg/kg, i.p.) 30 min before a 1h test with palatable food, rats begin to show appreciable levels of resting 10-15 min earlier than under control conditions (i.e. around 20 min versus 30-35 min into the session). The present results demonstrate that a 20 min increase in the injection-test interval (i.e. 50 min) had no significant impact on the anorectic, behavioural or weight gain effects of SB-334867 in non-deprived male rats. Most importantly, this altered treatment regimen led to a temporal profile of resting virtually identical to that previously observed with the more conventional 30 min injection-test interval. Although parallel studies indicated that the OX1R antagonist accelerated the onset of resting (and suppressed most active behaviours) even in the absence of food, an equianorectic dose of the natural satiety-related signal cholescystokinin octapeptide (CCK-8S; 5 microg/kg, i.p.) also produced very similar behavioural effects regardless of the presence of food. Together with evidence that SB-334867 preserves the structural integrity of natural feeding behaviour, does not induce nausea/illness or alter taste/palatability and fails to influence EEG measures of arousal/sleep, the present findings are consistent with the view that acute OX1R antagonism selectively enhances satiety. However, unlike the immediate short-circuiting of the satiety sequence induced by CCK-8S, the slower response to SB-334867 implies a more indirect mechanism of action.

    Topics: Analysis of Variance; Animals; Appetite; Behavior, Animal; Benzoxazoles; Body Weight; Drinking; Eating; Food Deprivation; Male; Naphthyridines; Nootropic Agents; Orexin Receptors; Rats; Reaction Time; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Satiety Response; Sincalide; Time Factors; Urea

2005
The proteasome inhibitor MG132 protects against acute pancreatitis.
    Free radical biology & medicine, 2005, Nov-01, Volume: 39, Issue:9

    The cell-permeant MG132 tripeptide (Z-Leu-Leu-Leu-aldehyde) is a peptide aldehyde proteasome inhibitor that also inhibits other proteases, including calpains and cathepsins. By blocking the proteasome, this tripeptide has been shown to induce the expression of cell-protective heat shock proteins (HSPs) in vitro. Effects of MG132 were studied in an in vivo model of acute pancreatitis. Pancreatitis was induced in male Wistar rats by injecting 2 x 100 microug/kg cholecystokinin octapeptide intraperitoneally (ip) at an interval of 1 h. Pretreating the animals with 10 mg/kg MG132 ip before the induction of pancreatitis significantly inhibited IkappaB degradation and subsequent activation of nuclear factor-kappaB (NF-kappaB). MG132 also increased HSP72 expression. Induction of HSP72 and inhibition of NF-kappaB improved parameters of acute pancreatitis. Thus MG132 significantly decreased serum amylase, pancreatic weight/body weight ratio, pancreatic myeloperoxidase activity, proinflammatory cytokine concentrations, and the expression of pancreatitis-associated protein. Parameters of oxidative stress (GSH, MDA, SOD, etc.) were improved in both the serum and the pancreas. Histopathological examinations revealed that pancreatic specimens of animals pretreated with the peptide demonstrated milder edema, cellular damage, and inflammatory activity. Our findings show that simultaneous inhibition of calpains, cathepsins, and the proteasome with MG132 prevents the onset of acute pancreatitis.

    Topics: Acute Disease; Amylases; Animals; Body Weight; Cysteine Proteinase Inhibitors; Cytokines; HSP72 Heat-Shock Proteins; Leupeptins; Lung; Male; NF-kappa B; Oxidative Stress; Pancreas; Pancreatitis; Pancreatitis-Associated Proteins; Proteasome Inhibitors; Rats; Rats, Wistar; Sincalide

2005
Overeating after restraint stress in cholecystokinin-a receptor-deficient mice.
    The Japanese journal of physiology, 2005, Volume: 55, Issue:5

    In mammals, including humans, a brain-gut hormone, cholecystokinin (CCK) mediates the satiety effect via CCK-A receptor (R). We generated CCK-AR gene-deficient (-/-) mice and found that the daily food intake, energy expenditure, and gastric emptying of a liquid meal did not change compared with those of wild-type mice. Because CCK-AR(-/-) mice show anxiolytic status, we examined the effects of restraint stress. Seven hours of restraint stress was found to significantly decrease both body weight and food intake during the subsequent 3 days in all tested animals. On the fourth day after restraint stress, the CCK-AR(-/-) mice showed a significantly higher level of daily food intake than prior to stress, and food intake recovered to prestress levels in the wild-type mice. Since peripheral CCK-AR has been known to mediate gastric emptying, both gastric emptying and gastric acid secretion were determined to examine the mechanism of overeating in CCK-AR(-/-) mice. Neither gastric emptying nor gastric acid secretion differed between CCK-AR(-/-) and wild-type mice on the fourth day after stress. In contrast, however, the contents of dopamine and its metabolites in the cerebral cortex of CCK-AR(-/-) mice were increased by stress, but were rather decreased in wild-type mice. Changes in 5-hydroxytryptamine (5-HT) and its metabolite 5HIAA did not differ between the genotypes. In conclusion, CCK-AR(-/-) mice showed overeating after restraint stress, and dopaminergic hyperfunction in the brain of these mice was observed. The present evidence suggests that the CCK-AR function, possibly via altering the dopaminergic function, might be involved in overeating after stress.

    Topics: Animals; Body Weight; Cholecystokinin; Eating; Gastric Acid; Gastric Emptying; Hormone Antagonists; Humans; Hyperphagia; Mice; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Sincalide

2005
The anti-inflammatory effect of methylprednisolone occurs down-stream of nuclear factor-kappaB DNA binding in acute pancreatitis.
    European journal of pharmacology, 2003, Mar-19, Volume: 464, Issue:2-3

    Glucocorticoids are potent anti-inflammatory drugs. The molecular mechanisms underlying these effects have not yet been fully revealed. The aim of the present study was to establish whether methylprednisolone pretreatment is beneficial and if it can block the pancreatic DNA binding of the transcription factor nuclear factor-kappaB (NF-kappaB) and proinflammatory cytokine synthesis during cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. Additionally, we set out to investigate the potential effects of methylprednisolone and CCK on pancreatic heat shock protein (HSP) synthesis. The dose-response (5-40 mg/kg) and time-course (6-72 h) curves of methylprednisolone on pancreatic HSP60 and HSP72 synthesis were evaluated following methylprednisolone treatment. We demonstrated that methylprednisolone specifically and dose-dependently induced HSP72 in the pancreas of rats, while it did not have a significant effect on HSP60 expression. The pancreatitis was induced near the peak level of HSP72 synthesis (2 x 30 mg/kg body weight [b.w.] methylprednisolone i.m. at an interval of 12 h, followed by a 12-h recovery period after the second injection of methylprednisolone) by administering 2 x 100 microg/kg CCK subcutaneously at an interval of 1 h. The injections of CCK in the vehicle-pretreated group significantly elevated the levels of pancreatic HSP60 and HSP72 2-4 h after the second CCK injection. Methylprednisolone pretreatment ameliorated many of the examined laboratory (the pancreatic weight/body weight [p.w./b.w.] ratio, the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic levels of tumor necrosis factor-alpha and interleukin-6, the degree of lipid peroxidation, protein oxidation, nonprotein sulfhydryl group content and the pancreatic myeloperoxidase activity) and morphological parameters of the disease. Methylprednisolone pretreatment did not influence pancreatic NF-kappaB DNA binding, but decreased proinflammatory cytokine synthesis in this acute pancreatitis model. The findings suggest that the anti-inflammatory effect of large doses of methylprednisolone in secretagogue-induced pancreatitis occurs downstream of NF-kappaB DNA binding, and that increased pancreatic HSP72 synthesis may play a role in the protective effect of the drug.

    Topics: Acute Disease; Amylases; Animals; Anti-Inflammatory Agents; Body Weight; Chaperonin 60; DNA; Dose-Response Relationship, Drug; Enzyme Activation; HSP70 Heat-Shock Proteins; I-kappa B Proteins; Interleukin-6; Lipid Peroxides; Male; Methylprednisolone; NF-kappa B; NF-KappaB Inhibitor alpha; Oligopeptides; Organ Size; Oxidation-Reduction; Pancreas; Pancreatitis; Peroxidase; Protein Binding; Proteins; Rats; Rats, Wistar; Sincalide; Sulfhydryl Compounds; Time Factors; Tumor Necrosis Factor-alpha

2003
Induction of HSP72 by sodium arsenite fails to protect against cholecystokinin-octapeptide-induced acute pancreatitis in rats.
    Digestive diseases and sciences, 2002, Volume: 47, Issue:7

    A number of investigators have demonstrated that the preinduction of heat-shock protein (HSP) expression (particularly HSP60 and HSP72) by hyper- or hypothermia may have a protective effect against cerulein-induced acute pancreatitis. The aim of the present study was to induce HSPs in the pancreas and lungs by thermal (hot-water immersion, HWI) and nonthermal methods (injection of sodium arsenite intraperitoneally) and to investigate the potential effects of HSP preinduction on cholecystokinin-octapeptide (CCK) induced acute pancreatitis and pancreatitis-associated lung injury in rats. The dose-response and time-effect curves observed following HWI and sodium arsenite treatments were evaluated. Animals were injected with 3 x 75 microg/kg CCK subcutaneously at intervals of 2 hr at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were killed by exsanguination through the abdominal aorta 2 or 6 hr after the last CCK injection. HWI and the injection of sodium arsenite significantly elevated the expression of HSP72 in the pancreas and lungs, whereas they did not influence the levels of HSP60. Overall, HWI pretreatment had a protective effect against CCK-induced pancreatitis and pancreatitis-associated lung injury. In contrast, the nonthermal preinduction of HSP72 by sodium arsenite did not result in any beneficial effects on the measured parameters of the disease. The findings suggest that the preinduction of HSP72 is not sufficient to protect against CCK-induced acute pancreatitis and pancreatitis-associated lung injury or that the beneficial effect of hyperthermia may not be exclusively related to HSP72 expression.

    Topics: Acute Disease; Amylases; Animals; Arsenites; Blotting, Western; Body Weight; Drug Combinations; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Immersion; Male; Organ Size; Pancreas; Pancreatitis; Rats; Rats, Wistar; Sincalide; Sodium Compounds

2002
Comparative effects of water immersion pretreatment on three different acute pancreatitis models in rats.
    Biochemistry and cell biology = Biochimie et biologie cellulaire, 2002, Volume: 80, Issue:2

    Cells respond to stress by upregulating the synthesis of cytoprotective heat shock proteins (HSPs) and antioxidant enzymes. The aim of this study was to compare the effects of cold (CWI) or hot water immersion (HWI) stress on three different acute pancreatitis models (cholecystokinin octapeptide (CCK), sodium taurocholate (TC), and L-arginine (Arg)). We examined the levels of pancreatic HSP60, HSP72, and antioxidants after the water immersion stress. Male Wistar rats were injected with CCK, TC, or Arg at the peak level of pancreatic HSP synthesis, as determined by Western blot analysis. HWI significantly elevated HSP72 expression and CWI significantly increased HSP60 expression in the pancreas. Water immersion stress decreased the levels of pancreatic antioxidants. CWI and-HWI pretreatment ameliorated most of the examined laboratory and morphological parameters of CCK-induced pancreatitis. CWI pretreatment decreased pancreatic edema and the serum amylase level; however, the morphological damage was more severe in TC-induced acute pancreatitis. Overall, CWI and HWI pretreatment only decreased the serum cytokine concentrations in Arg-induced pancreatitis. CWI and HWI resulted in differential induction of pancreatic HSP60 and HSP72 and the depletion of antioxidants. The findings suggest the possible roles of HSP60 and (or) HSP72 (but not that of the antioxidant enzymes) in the protection against CCK- and TC-induced acute pancreatitis. Unexpectedly, CWI pretreatment was detrimental to the morphological parameters of TC-induced pancreatitis. It was demonstrated that CWI and HWI pretreatment only influenced cytokine synthesis in Arg-induced pancreatitis.

    Topics: Acute Disease; Amylases; Animals; Antioxidants; Blotting, Western; Body Weight; Chaperonin 60; Cytokines; Disease Models, Animal; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Immersion; Lipase; Male; Microscopy, Electron; Organ Size; Pancreas; Pancreatitis; Rats; Rats, Wistar; Sincalide; Stress, Physiological; Trypsinogen

2002
Increased expression of gallbladder cholecystokinin: a receptor in prairie dogs fed a high-cholesterol diet and its dissociation with decreased contractility in response to cholecystokinin.
    The Journal of laboratory and clinical medicine, 2002, Volume: 139, Issue:5

    A series of our studies have shown that formation of cholesterol-supersaturated bile in patients with cholesterol gallstone disease is causatively related to decreased gallbladder contractility and mucin hypersecretion by the gallbladder. Supersaturated bile may modify the composition of gallbladder membranes so that the transduction of smooth muscle regulatory signals is impaired, and it may enhance the inflammation-induced mucin secretion by the gallbladder. To achieve a better understanding of the mechanism by which supersaturated bile impairs the contractility, we studied changes in the expression levels of gallbladder cholecystokinin (CCK-A) receptor messenger ribonucleic acid (mRNA) in prairie dogs fed a high-cholesterol diet. Levels of pathobiological determinants in arachidonate metabolism which are important for mucin secretion were also measured in their bile. Adult male prairie dogs were randomly assigned to receive either a semisynthetic diet (SSD) or an SSD plus 1.2% cholesterol (a high-cholesterol diet) for 2-, 4-, and 6-week periods. The contractile force in response to CCK-octapeptide (CCK-8) was measured by using gallbladder muscle strips. The mRNA levels of the CCK-A receptor were determined by reverse-transcription polymerase chain reaction (RT-PCR). Parallel to the increase in the cholesterol saturation index, the contractile responses to CCK-8 decreased in the animals fed a high-cholesterol diet for 4 weeks and markedly decreased in the animals with gallstone formation. However, in contrast to the decreased contractility, the steady-state mRNA levels of the gallbladder CCK-A receptor were significantly increased in the animals fed a high-cholesterol diet in comparison with the corresponding control animals. In the bile, a high-cholesterol diet caused an increase in the proportion of arachidonyl-phosphatidylcholine species, where phospholipase A(2) activity, prostaglandin E(2), and mucin concentrations were increased parallel to the feeding period. Up-regulation of the CCK-A receptor mRNA in the gallbladder of animals fed a high-cholesterol diet associated with decreased contractility may be due to an impairment of CCK signaling related to increased membrane cholesterol contents and its related reaction of biological compensation in order to increase the receptor concentration. The results of the present study suggest that in prairie dogs fed a high-cholesterol diet both a decrease in gallbladder contractility related to impairment of

    Topics: Animals; Arachidonic Acid; Bile; Blotting, Northern; Body Weight; Cholelithiasis; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, Dietary; Crystallization; Dinoprostone; Disease Models, Animal; Fatty Acids; Gallbladder; Gene Expression; Hydroxymethylglutaryl CoA Reductases; Lipids; Liver; Male; Microsomes, Liver; Mucins; Muscle Contraction; Muscles; Phosphatidylcholines; Phospholipases A; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sciuridae; Sincalide

2002
Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin.
    American journal of physiology. Regulatory, integrative and comparative physiology, 2001, Volume: 280, Issue:2

    Rats maintained on a high-fat (HF) diet exhibit reduced sensitivity to the satiation-producing effect of exogenous CCK. Because more CCK is released in response to HF meals than low-fat (LF) meals, we hypothesized that increased circulating CCK associated with ingestion of HF diets contributes to the development of decreased CCK sensitivity. To test this hypothesis, we implanted osmotic minipumps filled with either NaCl or CCK octapeptide into the peritoneal cavity. Subsequently, we examined the effect of intraperitoneal NaCl or CCK (0.5 microg/kg) injection on 30-min food intake. CCK significantly reduced 30-min food intake less in rats implanted with CCK-releasing minipumps compared with those with NaCl-releasing minipumps. Because dietary protein is a potent releaser of endogenous CCK, we hypothesized that rats adapted to a high-protein (HP) diet might also exhibit reduced sensitivity to exogenous CCK. Therefore, in a second experiment, we examined CCK-induced reduction of food intake in rats maintained on LF and rats maintained on HF or HP. Ingestion of LF stimulates very little endogenous CCK secretion, whereas both HF and HP markedly increase plasma CCK concentrations. Both doses of CCK reduced food intake significantly less in HF and HP rats compared with LF rats. There were no differences in 24-h food intake, body weight, or body fat composition among LF-, HF-, and HP-fed rats. These results are consistent with the hypothesis that sustained elevation of CCK either by infusion of exogenous CCK or by dietary-induced elevation of plasma CCK contributes to the development of reduced sensitivity to exogenous CCK.

    Topics: Adipose Tissue; Animals; Body Weight; Cholecystokinin; Dietary Fats; Dietary Proteins; Energy Intake; Infusions, Parenteral; Injections, Subcutaneous; Lipid Metabolism; Male; Rats; Rats, Sprague-Dawley; Satiation; Sincalide

2001
CCK peptides with combined features of hexa- and tetrapeptide CCK-A agonists.
    Journal of medicinal chemistry, 2000, Jun-15, Volume: 43, Issue:12

    Selective CCK-A agonist activity has been reported to induce satiety in a variety of animals, including man, and thereby suggests a therapeutic role for CCK in the management of obesity. To date, three general classes of CCK-A agonists have been reported, the full-length, sulfated hepta- and hexapeptides, a series of tetrapeptides, and most recently a series of benzodiazepines. The SAR of the hexa- and tetrapeptide classes suggests that the Hpa(SO(3)H) and Tac groups may not interact at the CCK-A receptor in the same location. However, the C-terminal dipeptide part of the hexapeptides and tetrapeptides appear to interact at the CCK-A receptor in a similar manner. Compound 7 (Hpa-Nle-Gly-Trp-Lys(Tac)-Asp-MePhe-NH(2)) derived from combining the features of the hexapeptides and the tetrapeptides has subnanomolar affinity and 3500-fold selectivity for CCK-A receptors. Compound 7 administered intraperitoneally produces potent, long-lasting reduction in food intake in rats and a corresponding weight loss when administered over nine consecutive days.

    Topics: Animals; Appetite Depressants; Binding, Competitive; Body Weight; Cerebral Cortex; Eating; In Vitro Techniques; Male; Oligopeptides; Pancreas; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Structure-Activity Relationship; Synaptosomes

2000
The vagus nerve is involved in the anorexigenic effect of simmondsin in the rat.
    Appetite, 2000, Volume: 34, Issue:2

    Simmondsin, 2-(cyanomethylene)-3 hydroxy 4,5 dimethoxy cyclohexyl beta-D-glucoside, from jojoba meal reduces food intake in rats. We investigated the mechanism of action simmondsin, by studying the effects of fasting or of vagotomy on the food intake reduction. The food intake reduction was significantly less in fasted rats than in non-fasted rats. The reduction of food intake was also significantly diminished after vagotomy. The results of the present experiments suggest that simmondsin reduces intake of food in rats through the augmentation of satiety, in part vagally mediated.

    Topics: Acetonitriles; Analysis of Variance; Animals; Anorexia; Appetite Depressants; Body Weight; Cyclohexanes; Eating; Fasting; Glucosides; Male; Nootropic Agents; Rats; Rats, Wistar; Sincalide; Vagotomy; Vagus Nerve

2000
Cholecystokinin and leptin act synergistically to reduce body weight.
    American journal of physiology. Regulatory, integrative and comparative physiology, 2000, Volume: 278, Issue:4

    Leptin, the product of the obese gene, reduces food intake and body weight in rats and mice, whereas administration of the gut-peptide CCK reduces meal size but not body weight. In the current experiments, we report that repeated daily combination of intracerebroventricular leptin and intraperitoneal CCK results in significantly greater loss of body weight than does leptin alone. However, leptin plus CCK treatment does not synergistically reduce the size of individual 30-min sucrose meals during this period, and the effect of leptin-CCK combination on daily chow intake, while significant, is small compared with the robust effects on body weight loss. This synergistic effect on body weight loss depends on a peripheral action of CCK and a central action of leptin. These data suggest a previously unsuspected role for CCK in body weight regulation that may not depend entirely on reduction of feeding behavior and suggest a strategy for enhancing the effects of leptin in leptin-resistant obese individuals.

    Topics: Adipose Tissue; Animals; Body Weight; Brain Chemistry; Carrier Proteins; Dietary Sucrose; Dose-Response Relationship, Drug; Drug Synergism; Eating; Injections, Intraperitoneal; Injections, Intraventricular; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Leptin; Satiation; Sincalide

2000
Iron deficiency diminishes gallbladder neuronal nitric oxide synthase.
    The Journal of surgical research, 2000, May-01, Volume: 90, Issue:1

    Iron deficiency has been demonstrated in the prairie dog to result in cholesterol crystal formation and altered biliary motility. Gallbladder filling and emptying are influenced by both inhibitory and excitatory stimuli, with nitric oxide (NO) playing a key role in normal relaxation. Iron is a cofactor for nitric oxide synthase. Therefore, we tested the hypothesis that iron deficiency would result in diminished levels of gallbladder neuronal nitric oxide synthase (nNOS) but would not influence the gallbladder's response to excitatory stimuli.. Twenty adult female prairie dogs were fed either an iron-supplemented (Fe(+)) (200 ppm) control diet (n = 10) or an iron-deficient (Fe-) (8 ppm) diet (n = 10) for 8 weeks. Fasting gallbladder volume was measured. Gallbladder muscle strips were harvested for response to excitatory stimuli and measurement of nNOS protein levels by Western blotting. Muscle strip response to a spectrum of doses of cholecystokinin, acetylcholine, and electrical field stimuli was determined, and the areas under the response curves were calculated.. Gallbladder volume increased in the iron-deficient prairie dogs compared with the iron-supplemented group (1.45 +/- 0.27 mL vs 0.80 +/- 0.13 mL, P < 0.05). Iron deficiency diminished the ratio of gallbladder nNOS to beta-actin protein levels (0.05 +/- 0.01 vs 3.48 +/- 1.02, P < 0.05) but resulted in a normal response to excitatory stimuli.. We conclude that diminished gallbladder neuronal nitric oxide synthase contributes to the gallbladder stasis that occurs with iron deficiency. This phenomenon may contribute to the increased incidence of gallstones in premenopausal women.

    Topics: Animals; Blotting, Western; Body Weight; Cholelithiasis; Cholesterol; Dogs; Female; Gallbladder; Iron Deficiencies; Muscle Contraction; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Sincalide; Transferrin

2000
Islet phospholipase A(2) activation is potentiated in insulin resistant mice.
    Biochemical and biophysical research communications, 2000, Jun-07, Volume: 272, Issue:2

    Insulin resistance is followed by an islet adaptation resulting in a compensating increase in insulin secretion and hyperinsulinemia. The mechanism underlying this increased insulin secretion is not established. We studied whether islet phospholipase A(2) (PLA(2)) contributes by using C57BL/6J mice fed a high-fat diet, since we previously showed that the insulin responses to the two PLA(2)-activating insulin secretagogues carbachol and cholecystokinin (CCK) are enhanced in this model. CCK (100 nM) and carbachol (100 microM) stimulated [(3)H]AA efflux, reflecting PLA(2) activation, both in islets from mice after 12 weeks on high-fat diet and in controls. The efflux increase was more pronounced in islets from high-fat diet-fed mice during both CCK (by 93 +/- 46%; P = 0. 034) and carbachol (by 64 +/- 22%; P = 0.009) stimulation. Also a direct PLA(2) activation by mellitin (2 microg/ml) elicited a potentiated efflux in islets from the insulin-resistant mice (by 361 +/- 107%; P = 0.002). The results suggest that exaggerated non-glucose-induced PLA(2) activation contributes to the islet compensation in insulin resistance.

    Topics: Animals; Arachidonic Acid; Blood Glucose; Body Weight; Carbachol; Diabetes Mellitus, Type 2; Dietary Fats; Enzyme Activation; Fatty Acids, Nonesterified; Female; Glucose; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Melitten; Mice; Mice, Inbred C57BL; Phospholipases A; Sincalide; Time Factors

2000
In vivo changes in the intestinal reflexes and the response to CCK in the inflamed small intestine of the rat.
    American journal of physiology. Gastrointestinal and liver physiology, 2000, Volume: 279, Issue:3

    Functional motor changes and morphological alterations have been associated with intestinal inflammation. The aim of our study was to evaluate functional alterations of intestinal reflexes and of the responses to CCK in the Trichinella spiralis model of intestinal inflammation. Rats were prepared with strain gauges and electrodes in the small intestine to evaluate spontaneous motor activity, the ascending contraction of the peristaltic reflex, and the motor responses to CCK-8 infusion. Infected animals showed increased motor activity at the duodenum and jejunum but not at the ileum. Ascending contraction was increased in both duodenum and ileum. Ascending excitation after N(omega)-nitro-L-arginine was still increased as well as the residual response after atropine. Response to CCK-8 during intestinal inflammation was changed in the jejunum, in which it turned from the inhibition shown in healthy animals to excitation. NADPH-diaphorase staining did not show any changes between distribution and density of positive neurons in either healthy or infected animals. In conclusion, intestinal inflammation induces functional changes in the motor activity that could explain the abnormal motor responses observed in inflammatory disorders.

    Topics: Animals; Body Weight; Eating; Enteric Nervous System; Interleukin-4; Interleukin-5; Intestine, Small; Male; NADPH Dehydrogenase; Nitric Oxide; Peristalsis; Rats; Rats, Sprague-Dawley; Sincalide; Trichinella spiralis; Trichinellosis

2000
Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice.
    Gastroenterology, 1999, Volume: 116, Issue:6

    Gastric emptying plays an important role in regulating food intake. This study was designed to investigate whether intraperitoneally injected urocortin reduces gastric emptying, feeding, and body weight in lean and ob/ob obese mice.. Food intake and body weight were measured after intraperitoneal injections of one of the following: urocortin, deamidated form of urocortin (urocortin OH), corticotropin-releasing factor (CRF), CRF6-33, cholecystokinin octapeptide (CCK-8), and leptin in 16-hour food-deprived animals. Gastric emptying was assessed 2, 4, or 8 hours after intraperitoneal injection. Repeated injections of urocortin were continued for 5 days in ob/ob mice.. Urocortin (0.003-3 nmol) dose-dependently and potently decreased food intake and body weight gain in lean mice. The ranking order of potency was urocortin > urocortin OH >/= CRF > CCK-8 > CRF6-33 > leptin. Gastric emptying was also potently reduced by urocortin with a similar ranking order of potency of urocortin > CRF > urocortin OH > CCK-8. Simultaneous administration of urocortin and CRF receptor antagonist, alpha-helical CRF9-41, blocked the effects of urocortin. Urocortin reduced food intake and body weight gain, as well as the rate of gastric emptying, in ob/ob mice, which was significantly faster than that of lean mice. Five daily injections of urocortin significantly lowered body weight and improved glycemic control in ob/ob mice.. The urocortin-induced decrease in food intake and body weight in lean and ob/ob mice is closely related to gastric emptying and opens new possibilities for the treatment of obesity.

    Topics: Animals; Blood Glucose; Body Weight; Corticotropin-Releasing Hormone; Dose-Response Relationship, Drug; Eating; Gastric Emptying; Injections, Intraperitoneal; Leptin; Male; Mice; Obesity; Proteins; Reference Values; Sincalide; Urocortins

1999
Cholecystokinin-8S levels in discrete hypothalamic nuclei of weanling rats exposed to maternal protein malnutrition.
    Regulatory peptides, 1999, Dec-23, Volume: 85, Issue:2-3

    Perinatal malnutrition and growth retardation at birth are suggested to be important risk factors for the development of overweight and syndrome X in later life. Underlying mechanisms are unknown. Body weight and food intake are regulated, e.g. by hypothalamic neuropeptidergic systems which are thought to be highly vulnerable to persisting malorganization due to perinatal malnutrition. To investigate possible consequences for hypothalamic cholecystokinin-8S (CCK-8S) in the offspring, pregnant Wistar rats were fed an 8% protein diet during pregnancy and lactation (low-protein group; LP) while control mothers (CO) received a 17% protein isocaloric standard diet. LP offspring displayed underweight at birth (P < 0.05) and during suckling (P < 0.001), while leptin levels were not altered. At weaning, under basal conditions CCK-8S was decreased in LP offspring in the paraventricular hypothalamic nucleus and arcuate hypothalamic nucleus (P < 0.05), as well as in the dorsomedial hypothalamic nucleus, lateral hypothalamic area and ventromedial hypothalamic nucleus (P < 0.01). In summary, these data indicate (1) an inhibition of the satiety peptide CCK-8S in main regulators of body weight and food intake in low-protein malnourished newborn rats; (2) no direct relationship of hypothalamic CCK-8S to circulating leptin at this age; and (3) no neurochemical signs of hypothalamic CCKergic dysregulation in this animal model at the age of weaning.

    Topics: Animals; Animals, Newborn; Birth Weight; Body Weight; Dietary Proteins; Disease Models, Animal; Eating; Female; Hypothalamus; Insulin Resistance; Male; Maternal-Fetal Exchange; Nutrition Disorders; Obesity; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar; Sincalide

1999
CCK stimulates growth of both the pancreas and the liver.
    International journal of surgical investigation, 1999, Volume: 1, Issue:1

    The pancreas is the main target of the trophic effect of cholecystokinin (CCK), with a transient increase in cell proliferation and persistent effect on DNA content and weight gain when given continuously. Whether CCK exerts similar effects on the liver and biliary tract is not known. Most studies on this subject have hitherto been done in the rat. The aim of the present experiments was therefore to study the possible concomitant trophic effects of CCK on these three organs in a gallbladder-bearing animal, the hamster.. CCK-8S or the CCK-A receptor antagonist devazepide were infused subcutaneously by osmotic minipumps for 4 weeks in 11 and 7 hamsters, respectively. Fifteen animals served as untreated controls. One hour before sacrifice tritiated thymidine was injected intraperitoneally. Plasma was collected for determination of CCK and the pancreas, liver, common bile duct and gallbladder were excised. The pancreas and liver were weighed and processed for the contents of protein, DNA and water. Tissue specimens were taken for autoradiography.. The concentration of CCK in plasma increased fourfold during the infusion of CCK-8S. The pancreas and, to a lesser extent, the liver increased in weight, DNA and protein contents after infusion of CCK-8S, whereas the pancreas, but not the liver, decreased in weight and protein content after infusion of devazepide. Pancreatic amylase content was increased after CCK-8S treatment, but unaffected by devazepide. Labelling index of pancreatic acinar cells, hepatocytes and gallbladder epithelium was no different from that of controls after four weeks of infusion of CCK-8S or devazepide. A correlation was found between the concentration of plasma CCK on one hand and the weights and DNA contents in pancreas and liver on the other.. The results suggest that CCK stimulates growth of both the pancreas and the liver in the hamster.

    Topics: Animals; Body Weight; Cholecystokinin; Cricetinae; Devazepide; Hormone Antagonists; Liver; Male; Organ Size; Pancreas; Sincalide; Thymidine

1999
Potentiated beta-cell response to non-glucose stimuli in insulin-resistant C57BL/6J mice.
    European journal of pharmacology, 1998, Jun-05, Volume: 350, Issue:2-3

    Insulin secretion in response to acetylcholine receptor activation by carbachol in insulin resistance induced by 12 weeks of high-fat diet in C57BL/6J mice is exaggerated. To study whether this persists after a longer period of time and also involves other non-glucose stimuli, we fed C57BL/6J mice a high-fat diet for 24 weeks. Both hyperinsulinemia (341 +/- 33 vs. 148 +/- 15 pmol/l) and slight hyperglycemia (7.8 +/- 0.2 vs. 6.1 +/- 0.1 mmol/l) were evident at this time point. The insulinotropic response to high dose carbachol (0.53 micromol/kg; 3403 +/- 377 vs. 1595 +/- 429 pmol/l), to the glucose analogue, 2-deoxyglucose (6 mmol/kg; 2014 +/- 315 vs. 1167 +/- 200 pmol/l), to cholecystokinin-8 (15.9 nmol/kg; 499 +/- 93 vs. 119 +/- 40 pmol/l) and to glucagon-like peptide-1 (32 nmol/kg; 307 +/- 86 vs. 71 +/- 9 pmol/l), were all exaggerated in mice given high-fat diet. In contrast, the insulin response to glucose was impaired. This shows that insulin resistance is accompanied by a general islet supersensitivity to non-glucose stimuli, which persists over a long period of time.

    Topics: Animals; Antimetabolites; Blood Glucose; Body Weight; Carbachol; Deoxyglucose; Diet; Female; Glucagon; Glucagon-Like Peptide 1; Glucose; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Mice; Mice, Inbred C57BL; Muscarinic Agonists; Peptide Fragments; Protein Precursors; Sincalide; Stimulation, Chemical

1998
Hormone replacement modifies cholecystokinin-induced changes in sucrose palatability in ovariectomized rats.
    Peptides, 1998, Volume: 19, Issue:6

    The taste reactivity test was used to examine the effect of CCK-octapeptide (CCK-8) on the palatability of a sucrose solution in ovariectomized rats either receiving hormonal replacement (estradiol and progesterone; OVX + HRT), or treated with vehicle only (OVX + VEH). Statistical analyses revealed that the OVX + HRT rats treated with CCK-8 exhibited a robust decrease in ingestive responses, and an increase in aversive responses and passive drips to the intraoral sucrose infusions, relative to treatment with the NaCl vehicle. In contrast, a weak effect of CCK-8 on ingestive responses, no significant effect on the frequency of aversive responses, and a reduced effect on passive drips was observed in the OVX + VEH rats. These results show that CCK-8 modifies sucrose palatability, and that this effect is modulated by gonadal hormone levels.

    Topics: Animals; Appetite; Body Weight; Drug Interactions; Eating; Estradiol; Female; Ovariectomy; Progesterone; Rats; Sincalide; Sucrose; Taste

1998
CCK-8 inhibits ingestive behavior in rats with lateral hypothalamic 6-OHDA lesions.
    Neuroreport, 1998, Aug-24, Volume: 9, Issue:12

    Male rats were injected with 6-hydroxydopamine in the lateral hypothalamus and tested for ingestive behavior starting on the day after the injection. The rats did not eat food pellets but readily ingested an intraorally infused nutritive solution. If given three daily intraoral infusions, 6-hydroxydopamine-treated rats defended their body weight and were as sensitive to the inhibitory effect of cholecystokinin octapeptide on intake as controls. Dopamine was reduced by 94% in the dorsal striatum five days after the 6-hydroxydopamine injection. Noradrenaline and serotonin were less markedly affected. Thus, while appetitive ingestive behavior is disrupted, consummatory ingestive behavior and body weight regulatory competence are only marginally affected by massive damage to forebrain dopamine neural networks.

    Topics: Animals; Biogenic Monoamines; Body Weight; Brain Chemistry; Depression, Chemical; Eating; Hypothalamic Area, Lateral; Male; Oxidopamine; Rats; Rats, Wistar; Sincalide; Sympathectomy, Chemical; Sympatholytics

1998
Reduction of cholecystokinin-8S-neurons in the paraventricular hypothalamic nucleus of neonatally overfed weanling rats.
    Neuroscience letters, 1998, Dec-11, Volume: 258, Issue:1

    Cholecystokinin (CCK) is suggested to be involved, e.g. in the central nervous modulation of food intake, possibly by acting within specific hypothalamic nuclei. Perinatal overnutrition predisposes to permanent obesity and hyperphagia, while underlying mechanisms are unclear. By reducing the litter size from the 3rd to 21st day of life, early overnutrition was induced in newborn rats. At weaning, clear overweight (P < 0.001), hyperglycaemia (P < 0.05), hyperinsulinaemia (P < 0.001), and insulin resistance (P < 0.001) occured. These early signs of obesity were associated with a significantly decreased number of CCK-positive neurons in the paraventricular hypothalamic nucleus (P < 0.002). In conclusion, due to neonatal overfeeding malformation of CCKergic neurons at the end of the critical hypothalamic differentiation period occurs. Long-term consequences on CCK-related neuroendocrine regulations could be suggested, including those affecting food intake and body weight gain.

    Topics: Animals; Animals, Newborn; Blood Glucose; Body Weight; Cell Count; Eating; Female; Immunohistochemistry; Insulin; Male; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Receptors, Cholecystokinin; Sincalide

1998
Synthesis and biological evaluation of potent, selective, hexapeptide CCK-A agonist anorectic agents.
    Journal of medicinal chemistry, 1997, Dec-19, Volume: 40, Issue:26

    Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp7 in conjunction with N-methylation of Phe8 produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Nle-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.

    Topics: Administration, Intranasal; Amino Acids; Animals; Appetite Depressants; Binding, Competitive; Body Weight; Dogs; Eating; Molecular Structure; Obesity; Oligopeptides; Peptides; Protein Binding; Rats; Receptor, Cholecystokinin A; Receptors, Cholecystokinin

1997
Effect of L364.718 during suckling on the sensitivity to the hypophagic effect of cholecystokinin in adult rats.
    Progress in neuro-psychopharmacology & biological psychiatry, 1997, Volume: 21, Issue:1

    1. In the present study it was investigated whether drugs acting at the cholecystokinin (CCK)-A receptor given to rat pups may result in long-lasting changes in body weight or regulation of food intake controlled by CCK. 2. From day 3 to day 10 of life, male and female Wistar rat pups were treated with the CCK-A receptor antagonist L-364.718 and the CCK-A + B agonist CCK-8S. 3. In adult rats, treated with L364.718 during suckling, the sensitivity to the acute hypophagic action of CCK-8S was weaker or abolished compared to adults treated with saline during suckling. In adult rats given CCK-8S during suckling acute treatment with CCK-8S reduced food intake to the same extent as in the group treated with saline postnatally. 4. These data show that early postnatal treatment with the CCK-A receptor antagonist L364.718 has an impact on the hypophagic response to CCK-8S in later life.

    Topics: Animals; Benzodiazepinones; Body Weight; Devazepide; Eating; Female; Hormone Antagonists; Male; Rats; Rats, Wistar; Receptors, Cholecystokinin; Sex Factors; Sincalide

1997
One-year treatment with cholecystokinin-octapeptide and secretin: effects on pancreatic trophism in the rat.
    Pharmacological research, 1997, Volume: 36, Issue:1

    The effects of long-term administration of cholecystokinin octapeptide (CCK-8) with or without secretin on the pancreas were examined in groups of rats treated with: (1) CCK-8 (1 microgram kg-1); (2) secretin + CCK-8 (1 microgram kg-1 of each); or (3) saline, administered subcutaneously twice daily for 5 out of 7 days for 6 or 12 months. A number of rats from all groups were studied for: (1) pancreatic size and biochemical composition (n = 6 for each group); (2) pancreatic secretion in the anesthetized state (n = 5 for each group); and (3) pancreatic histology (n = 6 for each group) after a 6-month treatment period. The rest of the animals treated for an additional 6-month period (n = 13 for each group) were examined for pancreatic size and histology. CCK-8 increased the weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor and amylase, but not that of lipase when given for 6 months, whereas administration of secretin + CCK-8 doubled the pancreatic content of lipase and increased all trophic parameters (except the amylase content) over those of CCK-8-treated rats. Maximum pancreatic volume and protein outputs in response to CCK-8 were higher in both of the hormone-treated groups than in the control; the sensitivity to the secretory action of CCK-8 was not altered. Pancreatic mass increased in response to either treatment after 12 months as well. Histological examination did not reveal pancreatic neoplasia in either group. The results indicate that long-term administration of CCK-8 or secretin + CCK-8 in rats results in sustained pancreatic hypertrophy and hyperplasia with secretory hyperfunction with no evidence of neoplastic alterations.

    Topics: Animals; Body Weight; Lipase; Male; Organ Size; Pancreas; Rats; Rats, Wistar; Secretin; Sincalide; Tropism

1997
A new biological contribution of cyclo(His-Pro) to the peripheral inhibition of pancreatic secretion.
    The American journal of physiology, 1997, Volume: 273, Issue:6

    The tripeptide pyro-Glu-His-Pro-NH2[thyrotropin-releasing hormone (TRH)] was isolated from the hypothalamus as a thyrotropin-releasing factor. It has a broad spectrum of central nervous system-mediated actions, including the stimulation of exocrine pancreatic secretion. TRH is also synthesized in the endocrine pancreas and found in the systemic circulation. Enzymatic degradation of TRH in vivo produces other bioactive peptides such as cyclo(His-Pro). Because of the short half-life of TRH and the stability of cyclo(His-Pro) in vivo, we postulated that at least part of the peripheral TRH effects on the exocrine pancreatic secretion may be attributed to cyclo(His-Pro), which has been shown to have other biological activities. This study determines in parallel the peripheral effects of TRH and cyclo(His-Pro) as well as the putative contribution of other TRH-related peptides on exocrine pancreatic secretion in rats. TRH and its metabolite cyclo(His-Pro) dose dependently inhibited 2-deoxy-D-glucose (2-DG)-stimulated pancreatic secretion. TRH and all the related peptides tested had no effect on the basal and cholecystokinin-stimulated amylase release from pancreatic acinar cells in vitro. These data indicate that cyclo(His-Pro) mimics the peripheral inhibitory effect of TRH on 2-DG-stimulated exocrine pancreatic secretion. This effect is not detected on isolated pancreatic acini. Our findings provide a new biological contribution for cyclo(His-Pro) with potential experimental and clinical applications.

    Topics: Amylases; Animals; Body Weight; In Vitro Techniques; Kinetics; Male; Pancreas; Peptide Fragments; Peptides, Cyclic; Piperazines; Rats; Rats, Wistar; Sincalide; Thyrotropin-Releasing Hormone

1997
Spontaneous and cholecystokinin-octapeptide-promoted regeneration of the pancreas following L-arginine-induced pancreatitis in rat.
    International journal of pancreatology : official journal of the International Association of Pancreatology, 1997, Volume: 22, Issue:3

    In L-arginine (Arg)-induced pancreatitis, evidence of acute inflammation was observed on d 1-3. Continuous tissue atrophy became visible at the sites of previous pancreatic necrosis, with simultaneous regeneration of the pancreas, mainly around the Langerhans islets. Administration of low doses of cholecystokinin-octapeptide (CCK-8) increased the inflammatory signs of pancreatitis in the early phase, but subsequently diminished the level of atrophy and accelerated the processes of regeneration in this model of pancreatitis.. The aim of this work was to study the regenerative processes following Arg-induced pancreatitis in rats. Besides the spontaneous regeneration, the effects of low doses of CCK-8 on the laboratory and morphologic parameters in this type of experimental pancreatitis were investigated.. Male Wistar rats were divided into three groups. In group I, the rats received 200 mg/100 g body weight of Arg i.p. twice, at an interval of 1 h, and 0.5 mL saline was administered s.c. twice daily. In group II, besides the same amount of Arg, the rats received 1 microgram/kg of CCK-8 s.c. in 0.5-mL saline twice daily (7 AM and 7 PM). In the control animals (group III), an identical amount of glycine was administered i.p. instead of Arg at the same times. The rats were examined on d 1, 3, 7, 14, and 28 after pancreatitis induction. The pancreatic weight/body weight ratio (pw/bw) was calculated in each case. The serum levels of amylase, and glucose and the pancreatic contents of soluble protein, trypsin, amylase and DNA were determined, and histologic examinations were performed.. In groups I and II, both pw/bw (3.5 +/- 0.2 mg/g and 4.1 +/- 0.28 mg/g, respectively) and the serum amylase level (8900 +/- 560 IU/L and 11100 +/- 1390 IU/L, respectively) were significantly elevated on d 1 vs group III (2.1 +/- 0.06 mg/g and 5562 +/- 373 IU/L, respectively). Pw/bw was significantly decreased in groups I (0.96 +/- 0.12 mg/g, 0.8 +/- 0.1 mg/g, and 1.8 +/- 0.1 mg/g, respectively) and II (1.4 +/- 0.15 mg/g, 1.7 +/- 0.2 mg/g, and 1.95 +/- 0.1 mg/g, respectively) on d 7, 14, and 28 vs group III (2.6 +/- 0.3 mg/g, 3.1 +/- 0.15 mg/g, and 2.7 +/- 0.1 mg/g, respectively), whereas in group II it was significantly elevated vs. group I on d 7 and 14. The pancreatic contents of soluble protein, DNA, trypsin and amylase were significantly decreased on d 3-14 in groups I and II vs group III. The pancreatic DNA level was significantly elevated in group II (1.23 +/- 0.2 mg/pancreas) vs group I (0.7 +/- 0.1 mg/pancreas) on d 7. In group II, the soluble protein (73.1 +/- 15.5 mg/pancreas) and amylase (1104 +/- 160 IU/pancreas) levels were significantly elevated on d 14 as was that of trypsin (27.2 +/- 3.1 IU/pancreas) on d 28, vs group I (26.4 +/- 5.3 mg/p, 525 +/- 111 IU/pancreas, and 16.3 +/- 1.1 IU/pancreas, respectively). On histologic sections, the signs of acute inflammation of the pancreas were more pronounced in group II than in group I on d 1-3. After that time, in spite of the progressive atrophy of the pancreas, the signs of tissue repair were more expressed in group II.

    Topics: Amylases; Animals; Arginine; Blood Glucose; Body Weight; DNA; Male; Organ Size; Pancreas; Pancreatitis; Proteins; Rats; Rats, Wistar; Regeneration; Sincalide; Trypsin

1997
Central implants of dilute estradiol enhance the satiety effect of CCK-8.
    Behavioral neuroscience, 1996, Volume: 110, Issue:4

    The following studies evaluated whether direct placement of estradiol into different brain areas could increase the satiating potency of CCK in female rats. In Experiment 1, estradiol implants in the PVN, but not in the VMN or third ventricle, significantly enhanced the satiety actions of CCK (5.0 micrograms/kg). In Experiment 2, a lower dose of CCK (0.5 micrograms/kg) suppressed food intake in females with estradiol implants in the PVN but not in animals with implants in the VMN or preoptic area. In both experiments, estradiol implants in the PVN significantly lowered food intake and body weight during the 2-day period of hormone treatment. Implants in other areas had no significant effects on feeding or body weight. These data support the hypothesis that the satiety effect of CCK is enhanced by estradiol and suggest that the PVN is involved in the interaction between CCK and estradiol.

    Topics: Animals; Body Weight; Brain Mapping; Drinking; Drug Implants; Drug Synergism; Eating; Estradiol; Female; Paraventricular Hypothalamic Nucleus; Rats; Satiety Response; Sincalide; Ventromedial Hypothalamic Nucleus

1996
Time-course changes in serum cytokine levels in two experimental acute pancreatitis models in rats.
    Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie, 1996, Volume: 196, Issue:3

    Activated leukocytes and cytokines have important roles in the multi-system involvement during acute pancreatitis. The changes in the serum level of tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) over time were investigated in two experimental acute pancreatitis models in rats. Mild edematous pancreatitis was induced with an overdose of cholecystokinin octapeptide (CCK-8), while a severe hemorrhagic form of pancreatitis was induced by ligation of the common bilio-pancreatic duct. The rats were examined 2, 4, 8, 16, 24 and 48 h after pancreatitis induction. The severity of the inflammation was assessed by measurement of the serum amylase activity, quantification of the edema, and histological examination. Serum TNF-alpha and IL-6 were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In CCK-8-induced acute pancreatitis, the pancreatic weight/body weight ratio (pw/bw) and amylase level were significantly elevated at 2 h, and the maximum levels were observed at 4 h (8.19 +/- 1.13 mg/g and 69.4 +/- 12.8 x 10(3) U/ml, respectively). Both parameters subsequently decreased continuously during the observation period. The serum IL-6 level was significantly increased at 4 h relative to the controls (123.3 +/- 5.8 vs 37.5 +/- 15 pg/ml), and then decreased continuously. In this model, only a moderate level of serum TNF-alpha was observed at 2 h. In the biliary type of acute pancreatitis, the ratio pw/bw increased continuously during the study and reached the maximum level at 48 h relative to the sham-operated control (8.8 +/- 1.4 vs 5.3 +/- 0.8 mg/g). The serum amylase level was significantly elevated at 2 h (43.2 +/- 13 x 10(3) U/ml), but then decreased continuously. The serum IL-6 reached its maximum level at 16 h (3800 +/- 447 pg/ml). In this model, increased TNF-alpha levels (75-300 U/ml) were measured 8, 16 and 24 h after pancreatitis induction. The results led to correlations between the serum IL-6 levels and the biochemical and morphological severity of acute pancreatitis in both experimental models. The data suggest that IL-6 and TNF-alpha may participate in the pathogenesis of these types of acute pancreatitis.

    Topics: Acute Disease; Amylases; Animals; Body Weight; Cholestasis; Disease Models, Animal; Interleukin-6; Laparotomy; Ligation; Male; Organ Size; Pancreatitis; Rats; Rats, Wistar; Sincalide; Time Factors; Tumor Necrosis Factor-alpha

1996
Interpretation of sham feeding data: curve-shift studies.
    The American journal of physiology, 1996, Volume: 271, Issue:4 Pt 2

    We explored the possibility that quantitative analysis of the relationship between sucrose concentration and sham intake differentiated how various treatments affected the intake of sweet solutions. Rats were sham fed sucrose solutions varying in concentration from 0.03125 to 1.5 M. Under different treatment conditions, intake concentration functions were generated that plotted amount sham fed against sucrose concentration. Sucrose concentration that yielded 50% maximal sham intake were calculated to indicate the position of the concentration-intake function on the x-axis. Quinine adulteration of sucrose solutions and injection of 0.5 mg/kg i.p. of the dopamine antagonist pimozide reduced sham intake and shifted the concentration-intake function to the right. Lithium chloride (60 mg/kg i.p.) injected 30 min before sham feeding, a reduction of food deprivation from 18 to 6 h before sham feeding, and 6 micrograms/kg cholecystokinin octapeptide reduced sham intake equivalent amounts but did not shift the concentration-intake functions along the x-axis. The data indicate that of several factors that reduce sham feeding, only some also shift the position of concentration-intake curves, and these curve shifts may identify intake changes mediated by alterations in the processing of the taste input.

    Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Drinking; Drug Combinations; Food Deprivation; Lithium Chloride; Male; Osmolar Concentration; Pimozide; Quinine; Rats; Rats, Inbred Strains; Sincalide; Solutions; Sucrose

1996
Intraventricular insulin enhances the meal-suppressive efficacy of intraventricular cholecystokinin octapeptide in the baboon.
    Behavioral neuroscience, 1995, Volume: 109, Issue:3

    Chronic intraventricular (IVT) insulin infusion suppresses food intake and body weight in the baboon. It has been hypothesized that one mechanism of this action may be enhancement of the effectiveness of satiety factors that regulate meal size. This hypothesis was supported by prior demonstration of a shift in the meal-suppressive effectiveness of cholecystokinin octapeptide (CCK-8) which was given intravenously. The authors tested the effectiveness of a near threshold dose of CCK-8 (25 ng/kg) given via the lateral ventricles (IVT) prior to a 30-min meal, while baboons were chronically infused with cerebrospinal fluid or insulin (100 microU/day) via the lateral ventricles. IVT CCK-8 infusion resulted in meal size changes of -44 +/- 7% and -75 +/- 9% in the absence and presence of insulin, respectively; this was observed in each of the three animals studied. These results provide further support for the hypothesis that IVT insulin can interact with other, meal-regulatory, peptides.

    Topics: Animals; Body Weight; Brain; Drug Synergism; Eating; Energy Intake; Injections, Intraventricular; Insulin; Male; Papio; Sincalide

1995
Odor-induced inhibition of intake after pairing of odor and CCK-8 in neonatal rats.
    Physiology & behavior, 1995, Volume: 57, Issue:1

    This study determined whether an odor that was paired with injections of CCK octapeptide would later come to inhibit independent feeding in neonatal rats. An odor so paired in rats that were not food or maternally deprived later reduced feeding during the infants' first independent feeding experience. Devazepide, the CCKA receptor antagonist, blocked the reduced intake when injected prior to the feeding test. These studies demonstrate that CCK is an effective unconditioned stimulus even when the animal is not eating during the conditioning process. Furthermore, the conditioned stimulus (the odor) causes behavioral change either by sensitizing a system that includes the CCKA receptor, by causing the release of endogenous CCK, or by changing some non-CCK system that enhances the processing of CCKA receptor-mediated information.

    Topics: Animals; Animals, Newborn; Body Weight; Conditioning, Classical; Dose-Response Relationship, Drug; Eating; Odorants; Rats; Rats, Sprague-Dawley; Sincalide

1995
Neurotrophic effects of testosterone on the medial nucleus of the amygdala in adult male rats.
    Journal of neuroendocrinology, 1994, Volume: 6, Issue:1

    Our previous reports of major sex differences in the substance P-immunoreactive (SPir) innervation of the medial posterior divisions of the bed nucleus of the stria terminalis (BST) and medial nucleus of the amygdala in rats raised the question of the hormonal regulation of this innervation. We now report the results of two experiments which examined the effects of castration of adult males on the SPir innervation of these regions. In experiment 2 we asked whether castration might also alter the cytoarchitecture of these regions. In experiment 1 three groups; sham operated (Sham), castrated (C) and castrated plus testosterone (C+T) were examined at each of the three survival periods (2, 4 and 8 weeks) post castration. Animals of the C+T groups each received a 45 mm silastic implant of testosterone sc at the time of castration to maintain testosterone levels postoperatively. Castration produced a consistent and highly significant decrease in the area of dense SPir fiber staining in the posterior medial amygdala which became greater with increasing survival. By 8 weeks the area of staining was 42% smaller in group C as compared to the matched sham-operated group. Smaller decreases were seen in the size of the dense field of SPir fibers in the posterior part of the dorsomedial BST. Testosterone implants maintained the size of the SPir fields of fibers in both the medial amygdala and BST, as the areas of staining in the C+T groups were not significantly different from those in the Sham groups at any of the 3 survival times. In experiment 2 we measured the area and optical density of SPir fiber staining in the medial amygdala and medial BST at 8 weeks post-castration. In addition, we measured the size of the cell groups within these regions using cresyl-stained sections. As in experiment 1, at 8 wks following castration there was a marked decrease in the area of dense SPir staining in both the BST and medial amygdala. The sizes of the dense fields of fibers were reduced by approximately 23% in the BST and by 40% in the posterior medial amygdala. Castration also significantly reduced the optical density of staining within the medial amygdala. The major finding of experiment 2 is that castration affects the cytoarchitecture as well as the SPir staining in these areas. In the BST, the cell group BSTMPM receives most of the dense SPir innervation.(ABSTRACT TRUNCATED AT 400 WORDS)

    Topics: Amygdala; Animals; Body Weight; Immunohistochemistry; Male; Orchiectomy; Organ Size; Rats; Rats, Sprague-Dawley; Sincalide; Substance P; Terminology as Topic; Testosterone

1994
Changes of cholecystokinin octapeptide tissue levels in rat brain following dopamine neuron lesions induced by 6-hydroxydopamine.
    Biological & pharmaceutical bulletin, 1994, Volume: 17, Issue:9

    Cholecystokinin octapeptide sulfated (CCK8) tissue levels in several regions of the rat brain were measured by amino terminal specific radioimmunoassay following the intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) to investigate the interaction between CCK8 and dopamine (DA). Pargyline and desmethylimipramine were administered 2 h before 6-OHDA injection. The levels of CCK8-like immunoreactivity in the frontal cortex, striatum, hippocampus, substantia nigra, and nucleus accumbens increased transiently on day 1 after 6-OHDA treatment. The levels in the frontal cortex, striatum and substantia nigra fell gradually to reach a subnormal level on day 7. In the nucleus accumbens, where the coexisting CCK8 and DA neurons lie, the tissue levels fell to a subnormal level on day 3. These decreased levels were unchanged until day 28. The irreversible destruction of DA neurons induced by 6-OHDA might cause drastic changes in regional CCK8-like immunoreactivity. The changes would depend on the neuromorphological differences in each structure. These results suggest that the CCK8 systems are closely related to the DA systems in several brain regions and that DA plays an important role in CCK8 release.

    Topics: Animals; Body Weight; Brain Chemistry; Chromatography, Gel; Dopamine; Injections, Intraventricular; Male; Neurons; Oxidopamine; Radioimmunoassay; Rats; Rats, Wistar; Sincalide

1994
Cyclic estradiol replacement increases the satiety effect of CCK-8 in ovariectomized rats.
    Physiology & behavior, 1994, Volume: 56, Issue:2

    The influence of cyclic ovarian hormone replacement therapy on the satiety effect of exogenous CCK-8 was determined to investigate the mechanism mediating the preestrous decrease in meal size in female rats. Once weekly, food-deprived ovariectomized rats were IP injected with 0.5-4 micrograms/kg CCK-8 and offered 0.4-0.8 M sucrose 52 h after the second of two daily SC injections of 2.5 or 10 micrograms estradiol benzoate or vehicle and 4 h after 500 mg progesterone or vehicle. In each of three tests, estradiol significantly increased CCK-8's inhibitory effect on sucrose intake. In contrast, progesterone alone or in combination with estradiol did not consistently influence the satiating potency of CCK-8. The interaction of estradiol and CCK-8 was clearest for the dose of 4 micrograms/kg CCK-8. The interaction occurred during diurnal tests and during dark-onset tests in which estradiol did not decrease baseline sucrose intake. These results demonstrate that a cyclic regimen of estradiol replacement in ovariectomized rats is sufficient to enhance the satiating effect of exogenous CCK-8 and that simultaneous progesterone treatment does not influence this effect. Potentiation of the satiating effect of CCK released from the small intestine by ingested food may be one of the mechanisms by which food intake decreases during the period of high estrogen concentration in the estrus cycle.

    Topics: Animals; Appetite; Body Weight; Dose-Response Relationship, Drug; Eating; Estradiol; Estrus; Female; Food Preferences; Ovariectomy; Rats; Rats, Sprague-Dawley; Satiety Response; Sincalide

1994
Cholecystokinin inhibits food intake at a peripheral extragastric site.
    Annals of the New York Academy of Sciences, 1994, Mar-23, Volume: 713

    Topics: Anastomosis, Roux-en-Y; Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Fasting; Feeding Behavior; Gastrectomy; Phenylurea Compounds; Rats; Receptors, Cholecystokinin; Sincalide; Time Factors

1994
Structural and functional changes of exocrine pancreas induced by FK506 in rats.
    Gastroenterology, 1993, Volume: 104, Issue:4

    The pancreas has been reported as a possible target for FK506 toxicity. This study was conducted to examine the effects of FK506 on the structure and function of pancreatic acinar cells.. Male Sprague-Dawley rats received an intramuscular injection of saline or FK506, and pancreatic acini were isolated on the day of sacrifice.. FK506 caused a time-dependent suppression in amylase secretory response to cholecystokinin or carbachol at days 3-14, and increases in amylase and trypsinogen content at days 7-14. The properties of cholecystokinin and scopolamine binding sites in acini were not altered by FK506. Amylase release by A23187 and secretin were decreased by FK506, but those by phorbol ester 12-O-tetradecanoylphorbol-13-acetate, forskolin, 5'-cyclic adenosine monophosphate and vasoactive intestinal peptide were not changed. Increases in cytosolic free calcium concentration induced by cholecystokinin were not changed by FK506. Histologically, a significant increase in cytoplasmic zymogen granules was observed in pancreas from FK506-treated rats.. These data suggest that FK506 induced changes in function and metabolism in pancreatic acinar cells, and these changes might be caused by altering postreceptor loci in stimulus-secretion coupling.

    Topics: Amylases; Analysis of Variance; Animals; Atropine; Body Weight; Calcimycin; Calcium; Carbachol; Cholecystokinin; Colforsin; Cytosol; Dose-Response Relationship, Drug; Feeding Behavior; Kinetics; Male; N-Methylscopolamine; Pancreas; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Reference Values; Scopolamine; Scopolamine Derivatives; Secretin; Sincalide; Tacrolimus; Tetradecanoylphorbol Acetate; Time Factors; Trypsinogen; Vasoactive Intestinal Peptide

1993
CSF cholecystokinin octapeptide in patients with bulimia nervosa and in normal comparison subjects.
    The American journal of psychiatry, 1993, Volume: 150, Issue:7

    Cholecystokinin octapeptide (CCK-8) appears to modulate appetitive behavior, and in rodents, anxiety-related behavior. The authors studied CCK-8 in patients with bulimia nervosa. CSF concentrations of CCK-8 were measured in 11 drug-free female patients with DSM-III-R-defined bulimia nervosa and in 16 normal subjects. The bulimic patients had significantly lower levels of CCK-8 than the comparison subjects. CCK-8 concentrations were inversely correlated with scores on the anger-hostility, anxiety, and interpersonal sensitivity subscales of the SCL-90-R. They were not significantly correlated with age, percentage of standardized average body weight, or mean weekly frequency of binge eating or vomiting. The results indicate that central CCK-8 abnormalities may play a role in the pathophysiology of bulimia nervosa.

    Topics: Adult; Age Factors; Body Weight; Bulimia; Eating; Female; Humans; Male; Psychiatric Status Rating Scales; Serotonin; Sex Factors; Sincalide

1993
Cholecystokinin octapeptide immunization: effect on growth of barrows and gilts.
    Journal of animal science, 1993, Volume: 71, Issue:9

    A study was conducted to validate the previously reported growth response to cholecystokinin octapeptide (CCK-8) immunization in barrows and was extended to include gilts. Group-penned barrows and gilts were used to represent conditions in the swine industry. Thirty-two animals, 19 barrows and 13 gilts, were randomly assigned by sex to four pens and two treatments. The control groups were immunized with human serum globulin (hSG). The treated groups (CCK) were immunized with the C-terminal octapeptide of cholecystokinin conjugated to human serum globulin. Specific binding of CCK-8 was confirmed at 29 d after the primary inoculation. Antisera titers were highly variable throughout. The mean titer reached a peak on d 57 and then declined. Body weight gains during the last 49 d, the period during which titers were expressed, were compared by ANOVA. The treatment effect on gain was significant (P = .018); the sex effect approached significance (P = .071); the treatment x sex interaction effect was not significant (P = .82). Least squares mean gain of the CCK group was 8.4% greater than of the hSG group, 41.4 vs 38.2 kg, respectively. A significant linear regression coefficient for gain vs antisera titer was obtained for barrows (P = .03; r2 = .44) but not for gilts. Several carcass variables showed trends similar to that of BW gain, but the treatment effects were less robust (P < .05 to .10). These results generally confirm the findings of the previous study; CCK-8 immunization stimulated growth of barrows by 7.5% in the present and by 10.8% in the previous study.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Analysis of Variance; Animals; Antibody Formation; Body Weight; Female; Immune Sera; Immunization; Least-Squares Analysis; Male; Meat; Random Allocation; Sex Factors; Sincalide; Swine

1993
Behavioral effects of A71623, a highly selective CCK-A agonist tetrapeptide.
    The American journal of physiology, 1992, Volume: 263, Issue:1 Pt 2

    We studied the behavioral effects of a novel cholecystokinin tetrapeptide (CCK-4) analogue, A71623, with full agonist activity and high affinity and selectivity for the CCK-A receptor subtype relative to the CCK-B receptor. In tests for anorectic activity, A71623 was found to suppress 60-min intakes of a liquid diet in both deprived and sated rats, and the effects were blocked by a selective CCK-A antagonist, A70104. Compared with CCK-8, A71623 was found to have improved potency and duration of action; the most potent route of administration was intraperitoneal. A71623 also suppressed the intake of a liquid diet and a 0.2 M sucrose solution in lean and obese Zucker rats. In daily injection studies, the anorectic activity of CCK-8 diminished rapidly, whereas the suppressant effects of A71623 on food intakes and body weight gains persisted throughout the 11-day treatment period. Finally, A71623 reduced the spontaneous locomotor activity of rats at doses above those required to suppress intakes. These studies are the first to describe the behavioral effects of a potent and highly selective CCK-A receptor agonist.

    Topics: Animals; Anorexia; Behavior, Animal; Body Weight; Cholecystokinin; Circadian Rhythm; Eating; Food Deprivation; Male; Motor Activity; Peptides; Rats; Rats, Inbred Strains; Sincalide; Tetragastrin; Time Factors

1992
The effect of cholecystokinin-octapeptide on food intake and consummatory behavior in lactating rats.
    Physiology & behavior, 1991, Volume: 50, Issue:2

    Rats are less sensitive to the satiating effect of CCK-8 during some reproductive states such as estrus and proestrus, and in ovariectomized rats following the administration of estradiol and progesterone. The sensitivity of rats to CCK-8's effect on food intake decreases as lactation progresses. During lactation, prolactin and progesterone levels are elevated. Implantation of ectopic pituitaries increases prolactin levels in males and females as well as progesterone levels in females. To evaluate whether or not prolactin elevation modifies CCK's effect on feeding, we studied the effect of CCK-8 on food intake during the early dark cycle in male and female rats implanted with ectopic pituitaries. As previously demonstrated, prolactin levels were elevated in both male and female pituitary-implanted rats and progesterone levels were elevated in the female rats. CCK-8 inhibited food intake in sham-operated male rats, but did not reliably decrease early dark cycle food intake in sham-operated or pituitary-implanted female rats or pituitary-implanted male rats. Thus an elevation in prolactin levels does not appear to modify the effect of CCK-8 on food intake in female rats. We also evaluated the effect of CCK on consummatory and maternal behavior in lactating rats. CCK-8 altered the meal patterns of lactating rats primarily by decreasing the rate of food consumption and increasing the latency to the first meal. The latency to the first meal of rats receiving CCK was increased during early and mid-lactation and the PW period, but not during late lactation compared to that of the saline-injected rats. CCK-8 did not modulate any of the maternal behaviors studied.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Animals; Arousal; Body Weight; Consummatory Behavior; Dose-Response Relationship, Drug; Eating; Female; Lactation; Pregnancy; Progesterone; Prolactin; Rats; Rats, Inbred Strains; Satiety Response; Sincalide

1991
Dynamic changes of pancreatic structure and function in rats treated chronically with nicotine.
    Toxicology and applied pharmacology, 1990, Volume: 104, Issue:3

    Adult, male Sprague-Dawley rats weighing initially 185-225 g, were treated with 5, 15, or 50 mg nicotine or placebo 3-week-release pellets by sc implantation, for 1.5, 3, 6 and 12 weeks. These doses of nicotine correspond to infusion rates of 9.9, 29.8, and 99.2 micrograms/h, respectively. At the highest nicotine dose trypsin and chymotrypsin activities were markedly higher in pancreas from 12-week nicotine-treated rats compared with controls. This was associated with a fourfold increase in steady-state amylase mRNA levels in comparison to placebo controls. In addition, secretagogue-stimulated enzyme release from pancreatic acini isolated from rats treated with 50 mg nicotine pellets was significantly higher than controls at 1.5 and 3 weeks and declined below control levels after 12 weeks of treatment. In rats treated with 15-mg nicotine pellets, maximal secretagogue-stimulated enzyme release from isolated acini occurred at 1.5 weeks, declining thereafter to control levels. Electron microscopy of pancreas from rats treated with the 50 mg nicotine dose revealed intracytoplasmic vaculoes appearing after 3 weeks of treatment, and persisting throughout the remaining experimental period. It is concluded that 12-week nicotine treatment results in increased pancreatic enzyme biosynthesis and accumulation of digestive enzymes within the pancreas. This is associated with altered responsiveness to secretagogues and evidence of morphological damage.

    Topics: Amylases; Animals; Blotting, Northern; Body Weight; Chymotrypsin; DNA; Dose-Response Relationship, Drug; Male; Nicotine; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; RNA; Sincalide; Trypsin; Trypsinogen; Vacuoles

1990
Effect of centrally and peripherally administered beta-endorphin on food intake in rats.
    International journal of peptide and protein research, 1989, Volume: 34, Issue:5

    A role for beta-EP in the regulation of food intake has been suggested as a contributory factor in the obesity of some genetically obese animal models. Studies undertaken to determine whether continuous administration of beta-EP could alter food intake in normal rats are described. The present studies demonstrated that continuous subcutaneous infusion with beta-EP was ineffective in modulating food intake, but that acute intraperitoneal or intracerebroventricular administration stimulated food intake in previously food deprived or satiated animals, respectively. These results suggest that beta-EP is not involved in the long-term regulation of food intake, but under certain conditions it may play some role in the regulation of individual meals. It is speculated that the latter activity may result from the action of other appetitive regulatory hormones.

    Topics: Animals; beta-Endorphin; Body Weight; Cerebral Ventricles; Eating; Infusion Pumps, Implantable; Infusions, Parenteral; Male; Rats; Rats, Inbred Strains; Sincalide

1989
Differential sensitivity of rat exocrine and endocrine pancreas to cyclosporine.
    Transplantation, 1988, Volume: 45, Issue:4

    The effect of 5, 10, and 20 mg/kg bw cyclosporine on rat endocrine and exocrine pancreatic function was studied. Glucose-dependent insulin secretion from the endocrine pancreas was shown to be significantly impaired 8 days after cyclosporine was given once daily at a dose as low as 5 mg/kg. CCK-8-stimulated amylase and lipase secretion were less sensitive to the noxious effect of cyclosporine being impaired at a dose of 10 mg/kg. Trypsin secretion was shown to be impaired at 20 mg/kg cyclosporine only. Our results demonstrate that cyclosporine causes dose-dependent impairment of both pancreatic endocrine and exocrine functions: the endocrine pancreas being more sensitive to the noxious action than the exocrine pancreas.

    Topics: Amylases; Animals; Behavior, Animal; Blood Glucose; Body Weight; Creatinine; Cyclosporins; Insulin; Insulin Secretion; Intubation, Gastrointestinal; Islets of Langerhans; Lipase; Male; Pancreas; Rats; Rats, Inbred Strains; Sincalide; Somatostatin; Trypsin

1988
Pancreatic endocrine function in cirrhotic rats.
    Metabolism: clinical and experimental, 1988, Volume: 37, Issue:9

    Pancreatic endocrine function in liver cirrhosis was examined in rats both in vivo and in vitro. Experimental liver cirrhosis was induced by subcutaneous injections of 50% carbon tetrachloride in a dose of 2 mL/kg body weight twice a week for 16 weeks. Control rats received a similar dose of olive oil during the same period. In cirrhotic rats, immunoreactive insulin contents in the pancreas were significantly lower, whereas immunoreactive glucagon contents were about threefold higher than those of control rats. In the first part of this study, insulin and glucagon concentrations in both jugular and portal venous blood at basal conditions and after oral glucose loading were simultaneously determined in vivo. Peripheral insulin levels, both before and after glucose loading, were higher, whereas portal insulin concentrations were lower in cirrhotic rats than in the control rats. In contrast, glucagon levels in both the peripheral and portal veins were significantly higher in cirrhotic rats than in control rats. In the second part, isolated perfused pancreata were prepared from cirrhotic and control rats to further characterize the endocrine function of cirrhotic rat pancreas. Insulin secretion in response to 16.7 mmol/L glucose and 100 pmol/L cholecystokinin-octapeptide both were 40% lower in cirrhotic rats than in controls. In contrast, there was no significant difference in arginine-stimulated insulin release between the two groups. However, glucagon secretion in response to 20 mmol/L arginine was 40% higher in cirrhotic rats. If sensitivity is defined as the hormone release proportional to the pancreatic contents, then A and B cells in the cirrhotic rats had normal sensitivity to both glucose and cholecystokinin-octapeptide.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Ammonia; Animals; Body Weight; Carbon Tetrachloride; Glucagon; Insulin; Islets of Langerhans; Liver Cirrhosis, Experimental; Male; Rats; Rats, Inbred Strains; Sincalide

1988
Facilitation of cancer-associated anorexia by cholecystokinin.
    Regulatory peptides, 1988, Volume: 20, Issue:2

    Cholecystokinin octapeptide (CCK-8, 5 micrograms/kg) was injected i.p. into male Sprague-Dawley rats bearing the Walker 256-carcinosarcoma, or into non-tumour bearing controls, on a 20-h food deprivation schedule. Food and water intake and body weight maintenance were monitored for 15 days after tumour implantation and compared to that of tumour-bearing animals not injected with CCK-8. Food intake was significantly reduced for the duration of the two 4-day periods of CCK-8 injection, indicating that behavioural tolerance to this peptide did not occur. The severity of anorexia and body weight loss in tumour-bearing animals was significantly greater than that observed in non-tumour bearing controls, for the first 13 days of observation. These results indicate that endogenous peptides, such as CCK, may function in tumour-bearing animals to enhance the anorexia and wasting which typifies the anorexia cachexia syndrome.

    Topics: Animals; Anorexia; Body Weight; Cachexia; Carcinoma 256, Walker; Drinking; Eating; Feeding and Eating Disorders; Male; Rats; Rats, Inbred Strains; Satiation; Sincalide

1988
Diet composition alters the satiety effect of cholecystokinin in lean and obese Zucker rats.
    Physiology & behavior, 1988, Volume: 43, Issue:4

    Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were maintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 micrograms/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p less than 0.001). Despite higher baseline caloric intakes (p less than 0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p less than 0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.

    Topics: Animals; Body Weight; Dietary Fats; Dose-Response Relationship, Drug; Energy Intake; Male; Rats; Rats, Zucker; Satiation; Satiety Response; Sincalide; Taste

1988
Effect of continuous infusions of CCK-8 on food intake and body and pancreatic weights in rats.
    The American journal of physiology, 1988, Volume: 254, Issue:1 Pt 2

    The ability of cholecystokinin (CCK) to act as a long-term satiety factor was assessed by its continuous infusion into the jugular veins of rats. Animals receiving a low dose of cholecystokinin octapeptide (CCK-8) (0.6 microgram CCK-8.kg body wt-1.h-1) did not show any significant differences in body weight changes or in food consumption from rats receiving saline and a group of unoperated controls over the 7-day infusion period. A 19.3-fold greater dose of CCK-8 (11.6 micrograms.kg body wt-1.h-1) did cause a significant decline in food consumption for the first 4 days compared with saline-infused rats (P less than 0.05) and unoperated controls (P less than 0.01). Rats receiving a high dose of CCK gained weight at a slower rate than rats receiving saline, but this effect lasted only 2 days and was not significant. Pancreatic growth was used as an indirect measure of elevated CCK levels in these animals. The infusion of 0.6 microgram CCK-8.kg body wt-1.h-1 did not lead to sufficiently elevated peptide levels to promote pancreatic growth. In contrast, those rats receiving a high dose of CCK-8 had significantly greater pancreatic weights (P less than 0.01) compared with saline-treated rats and unoperated controls. These results indicate that CCK-8, when administered continuously and in a large enough dose, can suppress food intake in rats for a period of several days before losing its effectiveness.

    Topics: Animals; Appetite; Body Weight; Eating; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Sincalide

1988
Chronic intraventricular administration of cholecystokinin octapeptide (CCK-8) suppresses feeding in rats.
    Brain research, 1988, May-17, Volume: 448, Issue:2

    Cholecystokinin octapeptide (CCK-8) is known to suppress feeding in sheep, pigs, golden hamsters and rats following acute intracerebroventricular (i.c.v.) injection. In this study, we report the effects of chronically administered i.c.v. CCK-8 on long-term food intake in rats. After baseline food intake was established over a period of 3 days, rats were implanted with Alzet osmotic minipumps, which delivered 1.0 microliter/h. Three groups of animals were prepared which received saline (vehicle) or CCK-8 at 12.25 micrograms/day (low dose) or CCK-8 at 122.5 micrograms/day (high dose). Surgical preparation of the animals with the intraventricular cannula and the osmotic minipump resulted in an initial reduction in food consumption in all groups. In the saline group daily food consumption returned to presurgery values by day 4. Similar results were observed with the low dose of CCK-8. In contrast, in animals receiving the high concentrations of CCK-8, the initial fall in feeding was more prominent and though it rose during the 7-day infusion interval, it remained statistically below control during this period. After termination of the infusion, daily food consumption rose to normal levels during the next 3 days. For comparison, the cumulative difference between daily food consumption over the period of 8 days during infusion and pre-infusion control was 39.9 +/- 10.0 g/24 h in the saline group. In CCK-8-infused animals, food consumption after pump implantation was reduced by an integrated value of 35.5 +/- 5.0 g/24 h at low dose and 117.4 +/- 20.2 g/24 h at high dose.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Animals; Body Weight; Brain; Circadian Rhythm; Dose-Response Relationship, Drug; Drinking Behavior; Feeding Behavior; Infusion Pumps; Injections, Intraventricular; Male; Rats; Rats, Inbred Strains; Sincalide

1988
A role for the area postrema in mediating cholecystokinin-stimulated oxytocin secretion.
    Brain research, 1987, Dec-01, Volume: 435, Issue:1-2

    We have investigated the role of the area postrema (AP) in mediating the neurohypophyseal hormone response to peripheral administration of nausea-producing agents in rats. In control animals, lithium chloride (LiCl) and apomorphine (APO) caused a rise in plasma levels of immunoreactive oxytocin (OT) and arginine-vasopressin (AVP), whereas sulphated cholecystokinin octapeptide (CCK-8s) stimulated OT secretion only. Rats with AP lesions exhibited a similar OT and AVP response to LiCl and APO but the OT response to CCK-8s was significantly diminished. The results indicate that the selective stimulation of OT secretion by CCK-8s is partly mediated via the AP. Although the nausea-producing effects of LiCl and APO may involve the AP, the neuroendocrine effects of these agents may well be mediated via actions outside the AP.

    Topics: Animals; Apomorphine; Arginine Vasopressin; Body Weight; Cerebral Ventricles; Chlorides; Lithium; Lithium Chloride; Male; Oxytocin; Rats; Rats, Inbred Strains; Sincalide

1987
Infusion of cholecystokinin between meals into free-feeding rats fails to prolong the intermeal interval.
    Physiology & behavior, 1987, Volume: 39, Issue:1

    The sulfated octapeptide of cholecystokinin (CCK-8) was infused intraperitoneally into 7 free-feeding male Sprague Dawley rats over a 6-day period. Infusions were given near the end of each free-feeding meal (1.87 microgram/meal/rat), and also during the intermeal interval in gradually increasing doses (0.10-0.63 microgram/5 min/rat). Food intake was continuously monitored and the infusions were controlled by microcomputer. Meal patterns, total food intake, and body weights during drug infusion were compared with data collected during a baseline period when only saline was infused. Meal-contingent CCK-8 infusion produced a significant 29.9% decrease in meal size which persisted throughout the drug-infusion period. Intermeal infusion of CCK-8 failed to prolong the intermeal interval (IMI) but it did initially prevent the compensatory decrease in IMI and increased feeding frequency expected after meal size was reduced. By the last day of drug infusion, total daily food intake recovered to baseline levels due to increased feeding frequency. Body weight was only transiently reduced by CCK-8 infusion. These findings show that tolerance does not develop to the action of CCK-8 to suppress meal size, and the administration of exogenous CCK-8 to free-feeding rats does not persistently prolong the intermeal interval.

    Topics: Animals; Body Weight; Feeding Behavior; Injections, Intraperitoneal; Male; Rats; Rats, Inbred Strains; Sincalide; Time Factors

1987
Ingestive behavior of rats with ibotenic acid lesions of the dorsomedial hypothalamus.
    The American journal of physiology, 1987, Volume: 252, Issue:5 Pt 2

    Rats with electrolytic or kainic acid (KA) lesions of the dorsomedial hypothalamic nucleus area (DMHA-L) are hypophagic, hypodipsic, and have a reduced body weight (BW) compared with controls. In the present study, male Sprague-Dawley rats received bilateral ibotenic acid (IBO) lesions of the DMHA (3 micrograms in 0.3 microliter) or sham (S) operations. During the next 32 days the IBO DMHA-L rats showed reduced (P less than 0.01) food and water intake, BW, and linear growth (P less than 0.03), although having a normal Lee obesity index. After a 24-h fast both groups became hyperphagic (P less than 0.01) with the DMHA-L group eating the most (P less than 0.01) during the 1st h; lost BW was regained at the same rate. In the absence of food, DMHA-L rats took less (P less than 0.01) water (data normalized) than S rats. During 24 h of water deprivation, both groups ate similar amounts of food (data normalized); following deprivation the groups were hyperdipsic. Both groups increased their food intake when given 300 mg/kg of 2-deoxy-D-glucose, which contrasts rats with electrolytic or KA DMHA-L rats. Both groups decreased their food intake when given cholecystokinin (3 micrograms/kg ip), which contrasts rats with electrolytic DMHA-L. The DMHA-L rats were not deficient in plasma glucose, insulin, growth hormone, or plasma Na+ and K+. Histology revealed many, but not all neurons, were destroyed in the DMN after IBO. The data indicate that IBO, electrolytic, or KA lesions of the DMHA produce similar but not identical physiological changes.

    Topics: Animals; Body Weight; Deoxyglucose; Eating; Feeding Behavior; Food Deprivation; Hypothalamus, Middle; Ibotenic Acid; Male; Rats; Rats, Inbred Strains; Sincalide; Water Deprivation

1987
Effects of kappa opiate agonists, cholecystokinin and bombesin on intake of diets varying in carbohydrate-to-fat ratio in rats.
    The Journal of nutrition, 1987, Volume: 117, Issue:5

    Effects of the dietary carbohydrate-to-fat ratio on opiate-stimulated eating and on naloxone-, cholecystokinin- and bombesin-suppressed eating were examined. Rats were fed either a high carbohydrate (cornstarch) diet (68% of energy from carbohydrate and 12% from fat), an intermediate diet (40% carbohydrate and 40% fat) or a high fat (corn oil and lard) diet (3% carbohydrate and 77% fat). Other rats self-selected from the high carbohydrate and high fat diets. Subcutaneous administration of naloxone, an opiate antagonist, generally suppressed intake of the high fat diet to a greater extent than intake of the high carbohydrate diet. Neither cholecystokinin octapeptide nor bombesin (administered intraperitoneally) exerted preferential suppression of fat intake. The opiate agonists ketocyclazocine and butorphanol tartrate administered subcutaneously at 1000 h preferentially, although not exclusively, stimulated intake of the high fat diet in a dose-dependent manner during the 6-h feeding trial. Repeated daily subcutaneous injections of butorphanol tartrate caused rats to consume more than 50% of their daily intake during the 6-h period postinjection; intake during the normal night feeding period was suppressed to maintain total daily intake equal to that of vehicle-injected rats. We conclude that stimulation of the opioid feeding system contributes to the overeating often associated with consumption of a high fat diet.

    Topics: Animals; Body Weight; Bombesin; Butorphanol; Cyclazocine; Dietary Carbohydrates; Dietary Fats; Eating; Energy Intake; Ethylketocyclazocine; Food Preferences; Male; Naloxone; Rats; Rats, Inbred Strains; Sincalide

1987
Effects of malnutrition and chronic reserpine treatment on pancreatic exocrine function.
    Pediatric research, 1986, Volume: 20, Issue:12

    The chronically reserpine-treated rat, an experimental model for cystic fibrosis, exhibits generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. Although chronic reserpine treatment induces malnutrition by decreasing food consumption and growth, the effects of this malnutrition per se on the exocrine pancreas have not been considered. In this study, the effects of chronic reserpine treatment and malnutrition on the exocrine pancreas were determined using pair-fed controls. Male, Sprague-Dawley rats were treated daily subcutaneously for 5 to 7 days with: no injection (control), 1.0 ml/kg vehicle or sham (control-sham, pair fed-sham), or 0.5 mg/kg reserpine (chronically reserpine-treated). Both chronic reserpine-treatment and pair-feeding significantly decreased food consumption (40%), body weight (51 and 59%), total pancreatic amylase (49 and 56%) and specific amylase activity (62 and 61%), pancreatic protein (65 and 75%), and pancreatic weights (62 and 65%) compared to controls. These decreases, however, were comparable between the chronically reserpine-treated and pair fed-sham rats. In contrast, the secretory response to the biologically active cholecystokinin analog cholecystokinin octapeptide was significantly attenuated in isolated pancreatic acini prepared from reserpine-treated rats compared to that from either control or pair-fed sham rats. Malnutrition decreased pancreatic amylase activity and protein comparably to reserpine treatment, but only partially attenuated the secretory response to cholecystokinin octapeptide. Based on the results of this study, pair-fed controls should be used to distinguish between the effects of reserpine alone and the induced malnutrition on pancreatic exocrine function in studies of this experimental model of cystic fibrosis.

    Topics: Amylases; Animals; Body Weight; Cystic Fibrosis; Disease Models, Animal; Eating; Lipase; Male; Nutrition Disorders; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Reserpine; Sincalide

1986
Effect of chronic intracerebroventricular infusion of cholecystokinin on respiration and sleep.
    Brain research, 1986, Jul-16, Volume: 378, Issue:1

    We investigated the effect of chronic intracerebroventricular infusion of the sulfated cholecystokinin octapeptide (CCK-8S) on sleep pattern and respiratory rate. The results indicate a depression of respiratory rate during Non-REM and REM sleep as well as an increase in the number of REM periods occurring per hour of Non-REM sleep. It is suggested that central release of CCK-8S is capable of modulating the automatic regulation of respiration during sleep and altering the normal sleep-waking pattern.

    Topics: Animals; Body Temperature; Body Weight; Injections, Intraventricular; Male; Rats; Rats, Inbred Strains; Respiration; Sincalide; Sleep; Sleep, REM

1986
Lesions of the area postrema and underlying solitary nucleus fail to attenuate the inhibition of feeding produced by systemic injections of cholecystokinin in Syrian hamsters.
    Physiology & behavior, 1986, Volume: 38, Issue:6

    A large body of evidence indicates that the intestinal hormone cholecystokinin (CCK) may serve as a signal for satiety. The abdominal vagus has been shown to be important for the satiety response to exogenous, and by inference, endogenous, CCK in rats and hamsters. Thus, it appears that stimulation of CCK receptors on afferent fibers of the abdominal vagus activates a gut-brain pathway to signal satiety. The present study was undertaken to further trace this viscerosensory pathway by examining food intake after administration of one of two doses (2.0 and 8.0 micrograms/kg) of CCK-octapeptide to intact hamsters and to hamsters sustaining lesions of the area postrema (AP) and underlying nucleus of the solitary tract (NST), regions containing neurons postsynaptic to vagal afferent fibers. As lesions of the AP/NST result in many alterations in ingestive behaviour and body weight regulation in rats, various aspects of feeding and drinking behaviour (spontaneous food intake, body weight maintenance, and responsiveness to a palatable drinking solution and osmotic stimulation) were also examined in lesioned hamsters. Aside from producing transient hypophagia and weight loss immediately after surgery, AP/NST lesions had no effects on these various parameters of ingestive behaviour. The lack of lesion effects on these particular parameters may be explained on the basis that hamsters are generally unresponsive to many of the stimuli for feeding and drinking which purportedly act on the vagus and/or AP/NST. Hamsters with AP/NST lesions were as responsive to the two tested doses of CCK as intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Animals; Body Weight; Cricetinae; Drinking; Eating; Female; Male; Medulla Oblongata; Mesocricetus; Saline Solution, Hypertonic; Sincalide; Vagus Nerve

1986
Effect of obstructive jaundice on amylase secretion in rat pancreatic acini.
    Gastroenterologia Japonica, 1985, Volume: 20, Issue:6

    The effect of obstructive jaundice on pancreatic amylase secretion was studied in isolated pancreatic acini prepared from bile duct ligated rats (7 days postoperatively), sham operated rats being used as control. Obstructive jaundice caused increase in pancreatic wet weight, pancreatic protein content and pancreatic amylase content by 27.9%, 40.1% and 33.2%, respectively. In acini prepared from obstructive jaundice group, compared with acini from sham operation group, responsiveness to cholecystokinin (CCK) and carbachol was decreased when amylase release was expressed as the percentage of total amylase activity initially present in acini. However, sensitivity to both secretagogues was unchanged when expressed as the percentage of maximally stimulated amylase release. The dose-response curves to Ca2+ ionophore for amylase release were similarly shaped in both groups. These results suggested that a pancreatico-trophic effect, compared with altered responsiveness of pancreatic acini, should play a major role in hypersecretion in obstructive jaundice.

    Topics: Amylases; Animals; Bilirubin; Body Weight; Calcimycin; Carbachol; Cholestasis; Male; Organ Size; Pancreas; Pancreatic Juice; Rats; Secretory Rate; Sincalide

1985
Relation between pancreatic growth and blood flow.
    The American journal of physiology, 1985, Volume: 248, Issue:1 Pt 1

    Male rats were treated with daily subcutaneous injections (3 micrograms/kg) of cholecystokinin octapeptide (CCK-OP), a synthetic CCK analogue, for 2, 4, 7, and 14 days, while control rats were injected with saline over the same intervals. Regional blood flows were measured with Sc46-labeled microspheres using the reference-organ method. Pancreatic wet and dry weights were determined in each treatment group. Total pancreatic DNA content was estimated with the diphenylamine reaction. Significant hyperplasia and increases in pancreatic wet weight occurred at 7 and 14 days, although hypertrophy was not evident in any of the treatment groups. No increases in small intestine wet weight or DNA content were evident in any treatment group. CCK-OP treatment induced a significant pancreatic hyperemia at 2 and 4 days of treatment. Pancreatic blood flow at 7 and 14 days was not different from control when expressed per unit tissue weight. The hyperemia seen at 2 and 4 days was not due to either a direct vascular effect of CCK-OP or an increase in pancreatic exocrine secretion. The hyperemia is therefore due to the growth stimulus and may be related to vasodilator metabolite accumulation during pancreatic tissue proliferation.

    Topics: Animals; Body Weight; DNA; Intestine, Small; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Regional Blood Flow; Sincalide

1985
Effect of chronic reserpine treatment on the pancreases of neonatal rats.
    Pediatric research, 1984, Volume: 18, Issue:12

    Chronic reserpine treatment of adult rats results in the accumulation of pancreatic enzymes and reduction of their discharge. These changes are reminiscent of those in cystic fibrosis. Since the majority of cystic fibrosis patients have their pancreatic dysfunction manifested in childhood, we studied chronic reserpine treatment in rat pups. Four-day-old rat pups were given reserpine (50 micrograms/kg intraperitoneally) or vehicle daily until sacrifice. The reserpine group showed significant decreases in body weights at 14 and 21 days of age. Pancreatic weights were also decreased but were of normal weight or increased when normalized against body weights. At 14 and 21 days of age, pancreatic concentrations of amylase, lipase, and trypsinogen showed no difference between reserpine and control pups. At both ages, pancreatic contents of all three enzymes were generally less in the treated pups, but were found to be similar when corrected for body weights. Hydrocortisone treatment of 14-day-old pups caused precocious accumulation of pancreatic enzymes in both reserpine and control groups. Intestinal contents of lipase, trypsin, and amylase were decreased in the reserpine pups at 14 days of age and reached a more significant level at 21 days of age; these data suggest a decrease in the secretion of pancreatic enzymes. Dispersed acini from 14-day-old pups showed a reduced capacity to release amylase as stimulated by carbachol or the octapeptide of cholecystokinin. The results suggested that chronic reserpine treatment of pups in the suckling period did not cause significant disturbance of the developmental accumulation of pancreatic enzymes. A definite inhibition of exocrine secretion was found with reserpine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Amylases; Animal Population Groups; Animals; Animals, Suckling; Body Weight; Carbachol; Female; Hydrocortisone; Lipase; Pancreas; Rats; Rats, Inbred Strains; Reserpine; Sincalide; Trypsinogen

1984
Decreased pancreatic CCK receptor binding and CCK-stimulated amylase release in Zucker obese rats.
    Physiology & behavior, 1984, Volume: 32, Issue:6

    In Zucker obese rats the response to the effects of CCK on food intake and pancreatic exocrine function are decreased. However, it is unknown whether the decreased responsiveness is due to decreased receptor number and/or sensitivity or abnormal circulating concentrations of CCK. In these experiments percent total binding of 125I-CCK-33 to pancreatic acini from obese rats was one-half that in lean rats when data was expressed on a per microgram DNA basis (19.6 +/- 5.1 vs. 47.4 +/- 11.4, p less than 0.01). In a second experiment while the maximally effective dose of CCK for stimulating amylase secretion from dispersed pancreatic acini was similar in obese and lean rats (10(-10) M), less amylase was secreted in obese rats across the dose range tested (p less than 0.001). In contrast, carbachol had similar potency and efficacy in stimulating amylase release from obese and lean pancreatic acini. The increase of pancreas size by use of a trypsin inhibitor was greater in lean than obese rats (p less than 0.03). In addition, stimulation of amylase release by CCK from obese trypsin inhibitor-treated compared with control obese rats was greater than that from lean trypsin inhibitor-treated compared with control lean rats (p less than 0.002). However, overall, stimulation of amylase secretion by CCK was only 36% of control (p less than 0.001) and by carbachol was only 20% of control (p less than 0.001). Thus, increased size by increased cell number was associated with decreased response per cell.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Amylases; Animals; Body Weight; Carbachol; Culture Techniques; DNA; Dose-Response Relationship, Drug; Esters; Female; Gabexate; Guanidines; Pancreas; Peptide Fragments; Rats; Rats, Zucker; Receptors, Cell Surface; Receptors, Cholecystokinin; Sincalide

1984
Role of gastrin and cholecystokinin in the ontogenic development of the gastrointestinal tract.
    Biology of the neonate, 1984, Volume: 45, Issue:2

    The role of gastrin and cholecystokinin (CCK) in postnatal development of the small intestine was examined in infant rabbits. Experimental animals received daily intraperitoneal injections of pentagastrin, 500 micrograms/kg, or CCK-octapeptide, 40 micrograms/kg, starting on day 3 of life. The animals were sacrificed at age 17-18 days. Weight and histologic sections of pancreas, stomach, duodenum, proximal jejunum, and ileum were obtained and mucosal lactase and sucrase activities determined in the intestinal segments. No differences were seen in any of the parameters assessed in pentagastrin-treated animals compared to saline-injected littermate controls. Body weight, weight and morphology of pancreas, stomach and intestinal segments, and enzyme activities did not differ significantly. Na+ transport in proximal jejunum under short-circuited conditions was not altered by pentagastrin. CCK-octapeptide also had no effect on weight or morphology of pancreas, stomach, and duodenum, but did lead to a significant increase in weight of proximal jejunum and ileum. Mucosal enzyme activities and morphometric measurements of villus height and mucosal thickness, however, did not differ significantly between CCK-octapeptide-treated animals and saline-injected littermate controls. The increase in weight of jejunal and ileal segments was reflected by an increase in thickness of the muscle layer. The findings indicate that neither gastrin nor CCK plays a role in the ontogenic development of the small intestine.

    Topics: Animals; Body Weight; Intestine, Small; Organ Size; Pancreas; Pentagastrin; Rabbits; Sincalide; Stomach

1984
Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats.
    The American journal of physiology, 1984, Volume: 246, Issue:5 Pt 2

    Food and water intake of free-feeding rats with indwelling intraperitoneal catheters connected to infusion pumps was continuously monitored and recorded by a microcomputer-based data acquisition system. Initially, at the start of every spontaneous meal for 4 days, each rat was infused with 0.27 ml of physiological saline. Saline infusion did not affect any feeding or drinking patterns, and the rate of weight gain remained unchanged. For 6 subsequent days, the octapeptide of cholecystokinin (CCK-8, 1.1 micrograms/meal) dissolved in physiological saline was infused at the onset of each meal. CCK-8 infusion caused a dramatic shift of patterns of food intake. Average meal size was reduced by at least 44%, whereas daily meal number increased by 162% or more for all 6 days of CCK-8 infusion. Total daily food intake recovered to predrug levels by the 4th day of CCK-8 infusion, primarily due to increased feeding frequency. Average body weight dropped by 12.4 g on the 1st day of CCK infusion, but over the following 5 days the growth rate was not different from the base-line predrug rate. With discontinuation of CCK-8 infusion all meal patterns returned rapidly to normal and body weight immediately recovered.

    Topics: Animals; Body Weight; Drinking; Drinking Behavior; Eating; Feeding Behavior; Male; Rats; Rats, Inbred Strains; Sincalide; Time Factors

1984
Amylase secretion by isolated pancreatic acini after chronic cholecystokinin treatment in vivo.
    The American journal of physiology, 1983, Volume: 244, Issue:6

    Rats were given subcutaneous injections of synthetic cholecystokinin octapeptide (CCK8, 5 micrograms/kg) in a depot carrier twice daily for 7-14 days. The pancreatic wet weight increased by 20.6 and 30.9% in the rats treated with CCK8 for 7 and 14 days, respectively. The increase in pancreatic weight was associated with an increase in the amount of protein per DNA, indicating hypertrophy of the acinar cells, and with an increase in the total amount of pancreatic DNA. Moreover, CCK administration also increased the amylase content per DNA. In acini prepared from CCK8-treated rats, responsiveness to CCK8 was increased when amylase release was expressed relative to DNA but was decreased when calculated as the percentage of the initial content in the acini. The dose-response curves for CCK8 were similarly shaped in both CCK8-treated and control rats, but they were shifted 3- to 10-fold toward higher concentrations of CCK8 after 7 and 14 days of CCK8 treatment. There were no major changes in the affinity and capacity of CCK receptors determined by studying the binding of radioiodinated CCK, suggesting that alterations in pancreatic amylase release were due to changes at a postreceptor loci. In support of this hypothesis, the secretory response to carbachol, known to act on a different receptor but by a common intracellular mechanism, was altered in a manner identical to the response to CCK8. Thus chronic stimulation with CCK sufficient to induce pancreatic hypertrophy does not greatly alter CCK receptors and induces only moderate postreceptor desensitization.

    Topics: Amylases; Animals; Appetite Depressants; Body Weight; Calcimycin; Carbachol; Cholecystokinin; Kinetics; Male; Organ Size; Pancreas; Peptide Fragments; Rats; Rats, Inbred Strains; Sincalide

1983
Rapid development of tolerance to the behavioural actions of cholecystokinin.
    Nature, 1983, Apr-21, Volume: 302, Issue:5910

    Cholecystokinin (CCK) acts acutely to inhibit food consumption in fasted rats, mice, sheep, pigs, monkeys and humans. CCK has been proposed as a satiety signal, inducing the behavioural sequence of satiety, or as an aversive internal stimulus, which inhibits food intake by inducing malaise. Reductions in food intake and related exploratory behaviours are initiated by CCK at its peripheral receptor in the gut, which appears to transmit sensory feedback via the vagus nerve to brain regions mediating appetitive behaviours. The therapeutic potential of CCK as an appetite suppressant in obesity syndromes rests on the demonstration of significant, long-lasting body weight reduction. Chronic CCK administration by repeated injections is problematic, since this peptide is rapidly degraded in vivo. We chose the Alzet constant infusion osmotic minipump to investigate possible alterations in body weight and food intake during continuous infusion of CCK. We now report that no change was detected in either body weight or total daily food consumption at any time point during 2 weeks of intraperitoneally (i.p.) infused CCK. The mechanism underlying the lack of chronic CCK effects appears to be a rapid development of behavioural tolerance. Acute challenge doses of CCK which induced satiety-related behaviours in saline-infused rats were ineffective in CCK-infused rats. The behavioural tolerance was apparent within a few hours of minipump implantation. These results provide the first evidence that rapid and reversible tolerance develops to the actions of a gut peptide.

    Topics: Animals; Appetite Depressants; Body Weight; Cholecystokinin; Drug Tolerance; Feeding Behavior; Male; Peptide Fragments; Rats; Rats, Inbred Strains; Sincalide

1983
Effects of cholecystokinin and secretin on intestinal structure and function.
    The American journal of physiology, 1983, Volume: 245, Issue:3

    Cholecystokinin and secretin are believed to be trophic gastrointestinal hormones. Studies were designed to determine whether these hormones exert their effect through stimulation of endogenous secretion. First, four groups of parenterally nourished rats underwent bypass of the proximal two-thirds of the intestine. One group received secretin, another cholecystokinin octapeptide (CCK-OP), another CCK-OP plus secretin, while the fourth group served as control. After 1 wk, animals were killed; pancreas and segments of intestine were removed. First, mucosal weight, protein content, and fatty acid esterification activity were affected only in intestine in continuity with endogenous secretions after hormone administration. Second, the effects of these hormones were tested in chow-fed rats. The hormone-treated group, despite pancreatic hyperplasia, had similar indexes of intestinal mass compared with pair-fed controls. We conclude that CCK-OP and secretin mediate their trophic effects on the small intestine indirectly, probably through stimulation of pancreatic secretion. In addition, the effects of luminal nutrients have complex interactions with these hormones.

    Topics: Animals; Body Weight; Cholecystokinin; Duodenum; Ileum; Intestinal Mucosa; Intestine, Small; Jejunum; Male; Organ Size; Pancreas; Peptide Fragments; Rats; Rats, Inbred Strains; Secretin; Sincalide

1983
Naloxone suppression of food and water intake and cholecystokinin reduction of feeding is attenuated in weanling rats with dorsomedial hypothalamic lesions.
    Physiology & behavior, 1983, Volume: 31, Issue:6

    In Experiment 1, sham operated (SCON) and dorsomedial hypothalamic nuclei (DMN) lesioned (L) rats were given saline or naloxone (0.1, 1.0 or 2.0 mg/kg) just prior to the onset of the dark cycle, lights out. Compared to saline injections, naloxone at all doses suppressed the cumulative food intake of the SCON during the second and third hr of measurement. Naloxone was without significant effect on the food intake of DMNL rats. Similar results were obtained in Experiment 2, except that naloxone at 2.0 mg/kg significantly suppressed the DMNL rats' food intake by the fourth hr of measurement. Cumulative water intake of both groups was significantly suppressed by naloxone in both experiments but its effects appeared to be attenuated in the DMNL group. In a preliminary trial cholecystokinin octapeptide (3.0 and 6.0 micrograms/kg) given at the onset of the dark cycle significantly suppressed the food intake of the SCON group but had no significant effect on the DMNL rats. The possibility exists that the reduced food intake and lower body weight of DMNL rats may partially result from damage to an opioid system. The data also tentatively suggest that DMN may play a role in cholecystokinin-induced satiety.

    Topics: Animals; Body Weight; Dorsomedial Hypothalamic Nucleus; Dose-Response Relationship, Drug; Drinking Behavior; Feeding Behavior; Hypothalamus, Middle; Male; Naloxone; Rats; Rats, Inbred Strains; Satiation; Sincalide

1983
Trophic effects of cholecystokinin octapeptide on the pancreas of the Syrian hamster.
    Canadian journal of physiology and pharmacology, 1982, Volume: 60, Issue:3

    Repeated subcutaneous injections of cholecystokinin octapeptide (CCK-OP) to Syrian golden hamsters for 10 days elicited a marked trophic effect on the pancreas, characterized by increased pancreatic weight and increased RNA/DNA ratios with an enhanced content of amylase in the pancreas in treated hamsters. These responses were observed after relatively small doses (100--300 ng CCK-OP x day-1 . 100 g body weight-1) of the hormone over a 10-day period. Although there was a small increase in total pancreatic DNA there was no definite evidence of hyperplasia in response to CCK-OP. DNA synthesis, as measured by histoautoradiography of tritiated thymidine labelled tissues, was increased in pancreatic acinar and islet cells, but not in ductal cells. This investigation, therefore, demonstrates a trophic action of CCK on the pancreas of the hamster similar to that reported for the rat and this may have relevance in studies of carcinogenesis since the hamster is an established species for studying pancreatic cancer.

    Topics: Amylases; Animals; Body Weight; Cholecystokinin; Cricetinae; DNA; Male; Mesocricetus; Organ Size; Pancreas; Peptide Fragments; RNA; Sincalide

1982
Obese mice and the satiety effects of cholecystokinin, bombesin and pancreatic polypeptide.
    Physiology & behavior, 1981, Volume: 26, Issue:3

    Topics: Animals; Body Weight; Bombesin; Cholecystokinin; Eating; Female; Mice; Mice, Obese; Pancreatic Polypeptide; Peptides; Satiation; Satiety Response; Sincalide

1981