devazepide and Body-Weight

CCK is hypothesized to inhibit meal size by acting at CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. Earlier studies have shown that obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic and obese. Recent findings show that rats with CCK1R-null gene on a Fischer 344 background (Cck1r(-/-)) are lean and normophagic. In this study, the metabolic phenotype of this rat strain was further characterized. As expected, the CCK1R antagonist, devazepide, failed to stimulate food intake in the Cck1r(-/-) rats. Both Cck1r(+/+) and Cck1r(-/-) rats became diet-induced obese (DIO) when maintained on a high-fat diet relative to chow-fed controls. Cck1r(-/-) rats consumed larger meals than controls during the dark cycle and smaller meals during the light cycle. These effects were accompanied by increased food intake, total spontaneous activity, and energy expenditure during the dark cycle and an apparent reduction in respiratory quotient during the light cycle. To assess whether enhanced responsiveness to anorexigenic factors may contribute to the lean phenotype, we examined the effects of melanotan II (MTII) on food intake and body weight. We found an enhanced effect of MTII in Cck1r(-/-) rats to suppress food intake and body weight following both central and peripheral administration. These results suggest that the lean phenotype is potentially driven by increases in total spontaneous activity and energy expenditure.

Topics: alpha-MSH; Animals; Body Weight; Devazepide; Eating; Energy Metabolism; Gene Deletion; Male; Models, Animal; Motor Activity; Peptides, Cyclic; Phenotype; Rats; Rats, Inbred F344; Rats, Mutant Strains; Receptor, Cholecystokinin A; Sequence Deletion; Thinness

We hypothesized that protein source in the nutritionally adequate AIN-93G diets fed during gestation, lactation, and weaning influences food intake (FI) regulation in male offspring of Wistar rats. Pregnant rats were fed the recommended casein-based (C) or soy protein-based (S) diet during gestation (experiment 1) or during gestation and lactation (experiment 2). Pups (n = 12 per group) weaned to C or S diets were followed for 9 wk (experiment 1) or 14 wk (experiment 2). At termination, body weight was 5.4% and 9.4% higher, respectively, in offspring of dams fed the S diet. Altered FI regulation was shown by failure of devazepide (a CCK-A receptor blocker) to block FI reduction after protein preloads in offspring of S diet-fed dams, whereas it had a strong effect on offspring of C diet-fed dams (P < 0.005). Similarly, naloxone (an opioid receptor blocker) blocked FI reduction more after casein than after soy protein preloads (P < 0.01). In experiment 2, offspring of dams fed the S diet had higher hypothalamic gene expression of agouti related protein at weaning (P < 0.05), and higher FI was found throughout postweaning (P < 0.0001). FI reduction after protein preloads at week 7 and after glucose preloads at week 13 was greater in offspring of C diet-fed dams (P < 0.05). Plasma insulin at weaning and insulin, ghrelin, and glucagon-like peptide-1 at week 15 were higher in offspring of S diet-fed dams (all P < 0.05). In conclusion, nutritionally complete C and S diets consumed during gestation and lactation differ in their effects on body weight and FI regulation in the offspring. Extending the diet from gestation alone to throughout gestation and lactation exaggerated the adverse effects of the S diet. However, the diet consumed postweaning had little effect on the outcome.

Topics: Agouti-Related Protein; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Appetite Regulation; Behavior, Animal; Body Weight; Caseins; Devazepide; Dietary Proteins; Female; Gestational Age; Ghrelin; Glucagon-Like Peptide 1; Hormone Antagonists; Hypothalamus; Insulin; Lactation; Male; Maternal Nutritional Physiological Phenomena; Naloxone; Narcotic Antagonists; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Receptor, Cholecystokinin A; Soybean Proteins; Time Factors; Weaning

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

Early life experience impacts emotional development in the infant. In rat pups, repeated, brief (i.e., 15 min) maternal separation (MS15) during the first 1-2 postnatal weeks has been shown to increase active maternal care and to reduce later anxiety-like behavior in the offspring. We hypothesized that the anxiolytic effect of MS15 is partly due to increased intestinal release of cholecystokinin (CCK) in rat pups as a result of increased maternal contact. We predicted that rats with a history of MS15 would display less anxiety in the elevated plus maze (EPMZ) and novelty-suppressed feeding (NSF) tests, as compared with nonseparated (NS) controls, and that the anxiolytic effect of MS15 would be attenuated in rats in which daily MS15 was accompanied by systemic administration of a CCK-1 receptor antagonist (i.e., devazepide). Treatment groups included NS control litters, litters exposed to MS15 from postnatal days (P)1-10, inclusive, and litters exposed to MS15 with concurrent subcutaneous injection of devazepide or vehicle. Litters were undisturbed after P10 and were weaned on P21. Subsets of adolescent males from each litter were tested in the EPMZ on P40-41, while others were tested for NSF on P50-52. As predicted, rats with a developmental history of MS15 displayed reduced anxiety-like behavior in the EPMZ and NSF tests. The anxiolytic effect of MS15 was preserved in vehicle-treated rats, but was reversed in devazepide-treated rats. These results support the view that endogenous CCK-1 receptor signaling in infants is a potential pathway through which maternal-pup interactions regulate the development and functional organization of emotional circuits that control anxiety-like behavior in the offspring.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Anxiety; Behavior, Animal; Body Weight; Cholecystokinin; Critical Period, Psychological; Devazepide; Exploratory Behavior; Feeding Behavior; Female; Hormone Antagonists; Male; Maternal Behavior; Maternal Deprivation; Rats; Receptors, Cholecystokinin

The ontogeny of the postingestive inhibitory control of intake by protein digestion products was investigated by administering gastric preloads of a peptone that was a hydrolysate of meat and that decreased intake in adult rats [Am. J. Physiol., Regul. Integr. Comp. Physiol. 276 (1999) R1623; Am. J. Physiol., Regul. Integr. Comp. Physiol. 277 (1999) R1144]. Gastric preloads of saline or peptone, or sham preloads were given 5 min before a 30-min, independent ingestion test in which pups had access to a sweet, high-fat milk diet. Preloads of isotonic peptone reduced intake significantly more than preloads of isotonic saline on postnatal day (P) 18, but not on P12. Pretreatment with the CCKA receptor antagonist devazepide (600 microg/kg ip) did not change the inhibitory effect of isotonic peptone. Thus, the inhibitory effect of peptone on P18 was apparently not mediated by endogenous CCK acting at CCKA receptors. In contrast to isotonic peptone, preloads of hypertonic peptone did not decrease intake more than preloads of hypertonic saline on P12, P18, or P24. We conclude that if the isotonic peptone used in these experiments is an adequate model of the digestion products of dietary protein at these postnatal ages, then the postingestive inhibitory control of intake by digestion products of dietary protein during independent ingestion appears between P13 and P18.

Topics: Age Factors; Animals; Animals, Newborn; Behavior, Animal; Body Weight; Devazepide; Drug Interactions; Eating; Feeding Behavior; Female; Hormone Antagonists; Isotonic Solutions; Male; Peptones; Postprandial Period; Rats; Rats, Sprague-Dawley; Saline Solution, Hypertonic; Satiety Response; Sodium Chloride; Time Factors

Proinflammatory cytokines released during the course of infection elicit numerous behavioral and metabolic changes. The decrease in food intake that accompanies infection is mediated in part by interleukin-1 (IL-1). Cholecystokinin (CCK) is a neuropeptide released during a meal, decreases food intake, and previous research suggests that CCK mediates the anorectic action of IL-1. The effects of estrogen on food intake are also thought to involve CCK, as the satiety action of CCK is increased by estradiol in both intact and ovariectomized rats. Estradiol also modulates many of the behavioral and physiological effects of IL-1. The present experiment examined the ability of the CCK(A) receptor antagonist devazepide to block the effects of IL-1 and estradiol on food intake in female rats. Adult animals were ovariectomized and given two daily subcutaneous injections of estradiol benzoate (EB; 5.0 microg) or the oil vehicle 3 weeks after surgery. Three days after treatment onset, animals were pretreated with devazepide or its vehicle 30 min prior to intraperitoneal injections of IL-1beta (4.0 microg/kg) or saline given 1 h before light offset. Food and water intake was measured following 2 h of spontaneous feeding. The results indicate that devazepide failed to reverse the anorectic action of IL-1beta, although the effects of estradiol on food intake were blocked by devazepide. These data do not support a role for CCK in IL-1-induced anorexia, and suggest that cytokines may act directly on neural systems involved in the control of food intake.

Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Devazepide; Drinking; Drug Interactions; Eating; Female; Hormone Antagonists; Interleukin-1; Ovariectomy; Rats; Rats, Long-Evans

The mouse W/Wv mutation of the c-Kit receptor causes extensive loss of gastrointestinal interstitial cells of Cajal and vagal intramuscular arrays (IMAs; one of the two putative mechanoreceptors in gastrointestinal smooth muscle). To characterize the behavioral phenotype of the c-Kit mouse and to evaluate the roles of these mechanoreceptors in controlling food intake, meal patterns and daily intakes of W/Wv mice and controls were examined using solid (20-mg pellets) and liquid (Isocal) maintenance diets. After the meal pattern experiments, CCK (0.5, 1, 2, 4, 8, and 16 microg/kg ip) was administered to examine the role of the interstitial cells and vagal IMA mechanoreceptors in relaying peripheral signals of satiety activated by CCK-A receptors, whereas the specificity of the response was assessed with the antagonist devazepide (300 microg/kg ip). On both diets, the W/Wv mice ate smaller meals for shorter durations, with a compensatory increase in meal number, resulting in daily intakes and body weights similar to the controls. After CCK injections, the mutant mice consistently suppressed intake more ( approximately 2x) in 30-min tests, regardless of the test diet (12.5% glucose, chow, pellets, and Isocal). The increased sensitivity of W/Wv mice to CCK reflected an increased potency of the hormone (c-Kit mouse ED50 = 2.4 microg/kg; control ED50 = 6.4 microg/kg) and a shift of the dose-response curve to the left. Devazepide blocked the CCK suppression of ingestion. These results indicate that the selective loss of the interstitial cells and IMAs disrupts short-term feeding of the W/Wv mice by inducing an earlier satiety, possibly by altering gastric accommodation and/or emptying, without affecting the long-term mechanisms controlling overall intake or body weight. The results also suggest that the reduction of interstitial cells and IMAs augments the sensitivity to or increases the efficiency of exogenous CCK.

Topics: Animals; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Eating; Enteric Nervous System; Feeding Behavior; Gastric Emptying; Gastrointestinal Motility; Hormone Antagonists; Male; Mice; Mice, Mutant Strains; Phenotype; Proto-Oncogene Proteins c-kit

Total gastrectomy often results in early satiety and loss of body weight. Serotonin inhibits food intake, and postprandial serotonin release is increased after total gastrectomy. Serotonin might contribute to early satiety and loss of body weight after total gastrectomy.. Food intake and body weight were investigated with an automated recording system in gastrectomized rats 1-12 months postoperatively. Rats were treated with metergoline, a 5-hydroxytryptamine (5-HT)(1/2) receptor antagonist, two different 5-HT(3) receptor antagonists, a combination of metergoline and devazepide, a cholecystokinin (CCK) a receptor antagonist, or vehicle. In addition, metergoline or vehicle was applied continuously by an intraperitoneal osmotic minipump for 7, 28, or 84 days after total gastrectomy.. Metergoline treatment resulted in a dose-dependent increase in food intake in gastrectomized rats. 5-HT(3) receptor antagonist treatment had no effect, and devazepide in addition to metergoline did not further stimulate food intake. Metergoline increased food intake at 1, 3, and 6 months postoperatively by up to 45% (24-h cumulative food intake [FI], 6 months: vehicle 3.83 +/- 0.10, metergoline 5.52 +/- 0.15 g/100 g body weight (BW), P < 0.0001). Chronic metergoline treatment for 7, 28, or 84 days significantly increased food intake after total gastrectomy compared to vehicle treatment (FI 7 days: vehicle 30.83 +/- 0.71, metergoline 36.27 +/- 0.85 g/100 g BW; P < 0.0002; average weekly FI during 28 days; vehicle 31.23 +/- 0.22, metergoline 36.83 +/- 0.33 g/100 g BW, P < 0.0001; average weekly FI during 84 days: vehicle 33.02 +/- 0.59, metergoline 35.07 +/- 0.48 g/100g BW, P < 0.008), and there was a significant body weight increase compared to vehicle treatment (7 days: DeltaBW vehicle -0.7 +/- 1.2 g vs DeltaBW metergoline 9.0 +/- 2.1 g, P < 0.001; 28 days: DeltaBW vehicle 0.3 +/- 2.2 vs DeltaBW metergoline 13.0 +/- 2.3, P < 0.001; 84 days: DeltaBW vehicle 25.7 +/- 10.2 vs DeltaBW metergoline 49.5 +/- 7.2, P < 0.04). Treatment for 84 days resulted in a significant body weight gain, while vehicle treatment had no effect (vehicle: 438 +/- 11 g vs 464 +/- 12 g, P < 0.2, n.s.; metergoline: 448 +/- 9 g vs 498 +/- 10 g, P < 0.007).. Inhibition of food intake by serotonin might contribute to early satiety and loss of body weight after total gastrectomy.

Topics: Animals; Body Weight; Devazepide; Drug Administration Schedule; Drug Combinations; Eating; Gastrectomy; Hormone Antagonists; Male; Metergoline; Postoperative Period; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Serotonin Antagonists

Feeding induces increased sleep in several species, including rats. The aim of the study was to determine if CCK plays a role in sleep responses to feeding. We induced excess eating in rats by 4 days of starvation and studied the sleep responses to refeeding in control and CCK-A receptor antagonist-treated animals. Sleep was recorded on 2 baseline days when food was provided ad libitum. After the starvation period, sleep was recorded on 2 refeeding days when the control rats (n = 8) were injected with vehicle and the experimental animals (n = 8) received intraperitoneal injections of L-364,718 (500 microg/kg, on both refeeding days). In the control group, refeeding caused increases in rapid eye movement sleep (REMS) and non-REMS (NREMS) and decreases in NREMS intensity as indicated by the slow-wave activity (SWA) of the electroencephalogram. CCK-A receptor antagonist treatment completely prevented the SWA responses and delayed the NREMS responses to refeeding; REMS responses were not simply abolished, but the amount of REMS was below baseline after the antagonist treatment. These results suggest that endogenous CCK, acting on CCK-A receptors, may play a key role in eliciting postprandial sleep.

Topics: Animals; Body Weight; Devazepide; Eating; Electroencephalography; Electromyography; Feeding Behavior; Food Deprivation; Injections, Intraperitoneal; Male; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Reference Values; Sleep; Sleep Stages; Sleep, REM

Food intake and meal size are reduced in female Long-Evans rats during estrus. To investigate the contribution of the satiating action of endogenous cholecystokinin (CCK) to this, rats were injected with 1 mg/kg of the potent, selective CCK(A) receptor antagonist, devazepide, during diestrus, when meal size is maximal, and during estrus, when it is minimal. Devazepide increased spontaneous food intake and meal size during estrus, but not during diestrus. Meal frequency was not affected by devazepide treatment. These results indicate that the potency of the CCK satiety-signaling system increases during estrus.

Topics: Animals; Body Weight; Cholecystokinin; Circadian Rhythm; Devazepide; Diestrus; Eating; Estrus; Feeding Behavior; Female; Hormone Antagonists; Motor Activity; Rats; Rats, Long-Evans; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Satiation

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

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

The genetically obese Zucker rat (fa/fa) is hyperphagic compared to lean controls (Fa/?). This hyperphagia is characterized by increased meal size. Cholecystokinin (CCK) has been shown to decrease meal size in many species including humans. In the present study we investigated the role of endogenous CCK in mediating the hyperphagia of male and female obese Zucker rats. CCKA-type receptors were blocked with the specific antagonist, devazepide, and test meal size was measured. Male obese and lean rats significantly increased food intake following devazepide. Neither obese nor lean female rats significantly increased food intake following devazepide. This is the first demonstration of a gender difference in endogenous CCK-mediated satiety. These results have implications for the higher incidence of eating disorders in females.

Topics: Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Eating; Energy Intake; Female; Male; Rats; Rats, Zucker; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Satiety Response; Sex Factors

Peripheral administration of the brain/gut peptide cholecystokinin (CCK) has been demonstrated to inhibit food intake in a variety of species, and administration of the specific type A CCK receptor antagonist devazepide increases food intake in a variety of experimental paradigms. The potency of CCK to inhibit intake depends upon a variety of factors, but CCK is generally less potent under conditions of elevated food intake. At different developmental stages, rats' intake requirements differ as growth rates change. To determine whether CCK plays a variable role in the control of intake in rats of different ages, we examined the feeding-inhibitory effect of various doses of CCK and the feeding-enhancing potential of various doses of devazepide on glucose consumption (0.5 kcal/ml) in male and female rats at 45-70 and 110-130 days of age. CCK was more potent in older male and female rats than in younger rats, and inhibited intake in a dose-related fashion. In younger rats, the efficacy of CCK was attenuated and the inhibition was not dose related. Administration of devazepide had no effect on intake in younger rats of either sex, but significantly increased glucose consumption in the older rats. These data suggest that during a period of rapid growth and high levels of food intake relative to body weight, adolescent rats are relatively insensitive to exogenous CCK and endogenous CCK does not appear to play a significant role in controlling their intake.

Topics: Age Factors; Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Eating; Energy Intake; Female; Male; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Satiety Response; Sex Factors

Meal patterns were recorded for 10.5 h in six lean and eight obese adult male Zucker rats after treatment with the cholecystokinin type A (CCKA) receptor antagonist, devazepide (750 micrograms/kg, IP, at 1330 h) or vehicle. In lean rats, devazepide significantly increased total food intake by 11%, average meal size by 35%, and meal duration by 49%. Devazepide also significantly decreased the average number of meals by 18%, although this was a smaller effect. Devazepide had none of these effects in obese rats. Devazepide treatment altered the meal pattern of lean rats so that it was similar to that of obese rats. These results demonstrate that endogenous CCK has a satiating effect in lean, but not in obese, male Zucker rats, which is the first demonstration of a loss of a physiological satiety signal in the obese Zucker rat. This defect could be due to: 1) a decrease in the release of endogenous CCK, 2) a decrease in the rate of CCK synthesis, or 3) the production of an abnormal form of CCK.

Topics: Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Feeding Behavior; Male; Rats; Rats, Zucker; Receptors, Cholecystokinin; Satiety Response

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

This study was undertaken to clarify the role of endogenous cholecystokinin (CCK) in induction of pancreatic growth stimulated by a high protein diet. Rats with i.v. jugular cannulae in place and kept in Bollman cages were adapted to 5% casein diet for 9 days and switched to 70% casein for 2 days. MK-329, a CCK receptor antagonist, and SMS 201-995, a somatostatin agonist, were continuously infused at 0.5 mg/kg/h and 5 micrograms/kg/h, respectively, starting at the onset of feeding 70% casein. The 5 and 70% casein control groups were infused with saline. Feeding 70% casein significantly stimulated pancreatic hyperplasia and tissue hypertrophy. MK-329 and SMS 201-995 totally prevented 70% casein-induced increases in pancreatic weight and total RNA and DNA contents. The results indicate that endogenous CCK is the major factor responsible for pancreatic growth induced by a high protein diet.

Topics: Amylases; Animals; Benzodiazepinones; Body Weight; Caseins; Cholecystokinin; Chymotrypsinogen; Devazepide; Dietary Proteins; DNA; Hyperplasia; Octreotide; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; RNA

We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

Topics: Animals; Benzodiazepinones; Bilirubin; Body Weight; Cholecystokinin; Cholestasis; Devazepide; Feeding Behavior; Male; Rats; Rats, Inbred Strains

To determine the type of cholecystokinin (CCK) receptor that mediates the inhibitory effects of peripherally administered CCK-8 on food intake and activity in 9- to 12-day-old rat pups, we gave injections of a type-A CCK receptor antagonist, MK-329, or of the type-B CCK receptor antagonist, L-365,260, prior to CCK-8 (IP). MK-329 reversed the inhibitory effects of CCK-8, but L-365,260 did not. This demonstrates that the inhibitory effects of CCK-8 (IP) are mediated by type-A, but not type-B, CCK receptors in pups of this age.

Topics: Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Feeding Behavior; Female; Motor Activity; Phenylurea Compounds; Pregnancy; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin

We examined whether endogenous cholecystokinin (CCK) is involved in growth of the preweanling rat pancreas. Twice daily for 14 days, 7-day-old neonatal rats received an oral gavage of either 2.5 mg/kg or 5.0 mg/kg of the potent and specific CCK receptor antagonist L-364,718 (the 2.5 mg/kg dose of antagonist was shown in the present study to abolish totally the pancreas growth-promoting effects of exogenously administered caerulein (CR) in neonatal rats). Control pups received oral gavages of the L-364,718 vehicle alone. The final body weights, pancreas weights, total pancreatic DNA contents, and total pancreatic protein contents did not differ significantly between the 21-day-old control pups and the 21-day-old pups that were pretreated for 14 days with either the low or the high doses of L-364,718. These findings suggest that endogenous CCK is not required for growth of the neonatal rat pancreas.

Topics: Amylases; Animals; Animals, Newborn; Benzodiazepinones; Body Weight; Ceruletide; Devazepide; DNA; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; Weaning