vasoactive-intestinal-peptide and Body-Weight

Reciprocal interactions closely connect energy metabolism with circadian rhythmicity. Altered clockwork and circadian desynchronization are often linked with impaired energy regulation. Conversely, metabolic disturbances have been associated with altered autonomic and hormonal rhythms. The effects of high-energy (HE) diet on the master clock in the suprachiasmatic nuclei (SCN) remain unclear.This question was addressed in the Sand rat (Psammomys obesus), a non-insulin-dependent diabetes mellitus (NIDDM) animal model. The aim of this work was to determine whether enriched diet in Psammomys affects locomotor activity rhythm, as well as daily oscillations in the master clock of the SCN and in an extra-SCN brain oscillator, the piriform cortex. Sand rats were fed during 3 months with either low or HE diet. Vasoactive intestinal peptide (VIP), vasopressin (AVP) and CLOCK protein cycling were studied by immunohistochemistry and running wheel protocol was used for behavioral analysis. High energy feeding dietary triggered hyperinsulinemia, impaired insulin/glucose ratio and disruption in pancreatic hormonal rhythms. Circadian disturbances in hyper-insulinemic animals include a lengthened rest/activity rhythm in constant darkness, as well as disappearance of daily rhythmicity of VIP, AVP and the circadian transcription factor CLOCK within the suprachiasmatic clock. In addition, daily rhythmicity of VIP and CLOCK was abolished by HE diet in a secondary brain oscillator, the piriform cortex. Our findings highlight a major impact of diabetogenic diet on central and peripheral rhythmicity. The Psammomys model will be instrumental to better understand the functional links between circadian clocks, glucose intolerance and insulin resistance state.

Topics: Animals; Biological Clocks; Body Weight; Brain; CLOCK Proteins; Diet; Dietary Fats; Dietary Fiber; Eating; Gene Expression Regulation; Gerbillinae; Insulin Resistance; Somatostatin; Vasoactive Intestinal Peptide; Vasopressins

In the present study, the therapeutic effects of Lactobacillus casei Qian (LC-Qian), the key microorganism in Tibetan yak yoghurt, on activated carbon-induced constipation were determined in vivo. ICR mice were treated with LC-Qian for nine days by oral administration. The body weight, defecation status, gastrointestinal transit and defecation time of mice were assessed, and the serum levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) were further evaluated. Bisacodyl was used as the positive control. The time until the first black stool defecation following carbon intake of the normal, control, 100 mg/kg bisacodyl-treated, Lactobacillus bulgaricus (LB)-treated, LC-Qian (L)-and LC-Qian (H)-treated mice was 93, 231, 121, 194, 172 and 157 min, respectively. Following treatment with LC-Qian, the gastrointestinal transit was increased to 52.4% [LC-Qian (L)] and 65.8% [LC-Qian (H)], while that in the group treated with the common lactic acid bacteria of LB was 40.3%. The MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and levels of SS were reduced in mice following LC-Qian treatment compared with those in the control mice (P<0.05). Reverse transcription quantitative polymerase chain reaction indicated that LC-Qian raised the c-Kit, GDNF as well as SCF mRNA expression levels and reduced the TRPV1 and NOS expression levels in tissue of the small intestine in mice. These results suggested that lactic acid bacteria prevent constipation in mice, among which LC-Qian was the most effective.

Topics: Acetylcholinesterase; Animals; Body Weight; Carbon; Constipation; Defecation; Endothelins; Female; Gastrins; Gastrointestinal Transit; Gene Expression; Glial Cell Line-Derived Neurotrophic Factor; GPI-Linked Proteins; Intestine, Small; Lacticaseibacillus casei; Mice; Mice, Inbred ICR; Motilin; Probiotics; Proto-Oncogene Proteins c-kit; Somatostatin; Substance P; TRPV Cation Channels; Vasoactive Intestinal Peptide

Arterial hypertension is associated with serious dysfunction of the cardiovascular system and digestive system. Given the relevant role of vasoactive intestinal peptide (VIP) in the regulation of digestion process, control of blood pressure and heart rate as well as cardio- and gastro-protective character of the peptide, it appeared worthwhile to undertake the research aimed at immunohistochemical identification and evaluation of VIP-positive structures in the pylorus and heart of hypertensive rats. Up to now, this issue has not been investigated. The experimental model of hypertension in rats according to Goldblatt (two-kidney one clip model of hypertension) was used in the study. The experimental material (pylorus and heart) was collected in the sixth week of the study. VIP-containing structures were evaluated using immunohistochemical and morphometric methods. The analysis of the results showed a significant increase in the number of immunoreactive VIP structures and in the intensity of immunohistochemical staining in the stomach and in the heart of hypertensive rats. Our findings indicate that VIP is an important regulator of cardiovascular and digestive system in physiological and pathological conditions. However, to better understand the exact role of VIP in hypertension further studies need to be carried out.

Topics: Animals; Blood Pressure; Body Weight; Disease Models, Animal; Gastric Mucosa; Gene Expression Regulation; Heart Rate; Hypertension, Renovascular; Immunohistochemistry; Inflammation; Male; Myocardium; Rats; Rats, Wistar; Tissue Distribution; Vasoactive Intestinal Peptide

The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1×10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1×10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.

Topics: Acetylcholinesterase; Animals; Body Weight; Carbon; Constipation; Defecation; Endothelins; Feces; Female; Gastrins; Gastrointestinal Transit; Laxatives; Limosilactobacillus fermentum; Mice, Inbred ICR; Motilin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Y-receptors control energy homeostasis, but the role of Npy6 receptors (Npy6r) is largely unknown. Young Npy6r-deficient (Npy6r(-/-)) mice have reduced body weight, lean mass, and adiposity, while older and high-fat-fed Npy6r(-/-) mice have low lean mass with increased adiposity. Npy6r(-/-) mice showed reduced hypothalamic growth hormone releasing hormone (Ghrh) expression and serum insulin-like growth factor-1 (IGF-1) levels relative to WT. This is likely due to impaired vasoactive intestinal peptide (VIP) signaling in the suprachiasmatic nucleus (SCN), where we found Npy6r coexpressed in VIP neurons. Peripheral administration of pancreatic polypeptide (PP) increased Fos expression in the SCN, increased energy expenditure, and reduced food intake in WT, but not Npy6r(-/-), mice. Moreover, intraperitoneal (i.p.) PP injection increased hypothalamic Ghrh mRNA expression and serum IGF-1 levels in WT, but not Npy6r(-/-), mice, an effect blocked by intracerebroventricular (i.c.v.) Vasoactive Intestinal Peptide (VPAC) receptors antagonism. Thus, PP-initiated signaling through Npy6r in VIP neurons regulates the growth hormone axis and body composition.

Topics: Adiposity; Animals; Body Weight; Corticosterone; Diet; Energy Metabolism; Feeding Behavior; Fertility; Homeostasis; Insulin-Like Growth Factor I; Ligands; Mice; Mice, Inbred C57BL; Obesity; Pancreatic Polypeptide; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide Y; Signal Transduction; Suprachiasmatic Nucleus; Thinness; Vasoactive Intestinal Peptide

Gonadotropin-releasing hormone (GnRH) analogs are given to women undergoing in vitro fertilization. Case reports describing the development of chronic intestinal pseudo-obstruction and auto-antibodies against GnRH after such treatment suggest a strong association between intestinal dysfunction and GnRH analogs. No experimental model for studying such a relationship is currently at hand. Our main goal was to investigate possible enteric neurodegeneration and titers of GnRH antibodies in response to repeated administration of the GnRH analog buserelin in rat. Rats were treated for 1-4 sessions with daily subcutaneous injections of buserelin or saline for 5 days, followed by 3 weeks of recovery. Buserelin treatment caused significant loss of submucous and myenteric neurons in the fundus, ileum, and colon. The loss of enteric neurons can, at least partly, be explained by increased apoptosis. No GnRH- or GnRH-receptor-immunoreactive (IR) enteric neurons but numerous luteinizing hormone (LH)-receptor-IR neurons were detected. After buserelin treatment, the relative number of enteric LH-receptor-IR neurons decreased, whereas that of nitric-oxide-synthase-IR neurons increased. No intestinal inflammation or increased levels of circulating interleukins/cytokines were noted in response to buserelin treatment. Serum GnRH antibody titers were undetectable or extremely low in all rats. Thus, repeated administrations of buserelin induce neurodegeneration in rat gastrointestinal tract, possibly by way of LH-receptor hyperactivation. The present findings suggest that enteric neurodegenerative effects of GnRH analog treatment in man can be mimicked in rat. However, in contrast to man, no production of GnRH auto-antibodies has been noted in rat.

Topics: Animals; Apoptosis; Body Weight; Buserelin; Cell Count; Cell Survival; Colon; Female; Gastrointestinal Tract; Gonadotropin-Releasing Hormone; Immunohistochemistry; Intestinal Mucosa; Male; Neurons; Nitric Oxide Synthase Type I; Rats; Rats, Sprague-Dawley; Receptors, LH; Receptors, LHRH; Vasoactive Intestinal Peptide

Lizhong Pill, composed of radix Ginseng (Panax ginseng C.A. Meyer), rhizoma Zingiberis (Zingiber officinale Roscoe), rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.) and radix Glycytthizae (Glycyrrhiza uralensis Fisch.), is a classical herbal product for curing spleen deficiency in traditional Chinese medicine (TCM), and reserpine treated rats show similar signs to TCM spleen deficiency pattern. This paper is aimed to explore the regulatory effect on neuroendocrinoimmune network by Lizhong Pill in reserpine induced TCM spleen deficiency rats.. 100 healthy adult male SD rats, with a mean weight of 200 g, were randomly divided into five groups in average: control group, reserpine treated group, atropine treated group, treatment groups with Lizhong Pill at high dose and low dose (equal to the dosage of crude drugs for 4 g/kg/d and 8 g/kg/d). Rats in reserpine treated group were induced by intraperitoneal injection of reserpine at 0.5 mg/kgd for 4 weeks. The levels of IL-1, IL-6 and gastrin were measured with radioimmunoassay, TNF-α and IFN-γ in serum were measured with ELISA, the level of vasoactive intestinal peptide (VIP) and substance P (SP) in small intestine were determined with radioimmunoassay, and the TNF-α and TGF-β positive cells in small intestine were detected by immunohistological staining. Data were analyzed with SAS 9.1 software package.. The rats in reserpine treated group, body weight, concentrations of IFN-γ, IL-1 and TNF-α in serum, expression of TGF-β in small intestine, VIP in small intestine decreased (P<0.05), and the level of IL-6 in serum, expression of TNF-α, SP in small intestine and gastrin were increased (P<0.05). Administration of Lizhong Pill at high dose could increase the body weights at day 21, and the weights of rats in Lizhong Pill groups were much higher compared to reserpine treated group. At high dose of Lizhong Pill could increase the level of TNF-α in serum. Lizhong Pill at high dose and low dose could reverse the changes of IL-1, IL-6 and IFN-γ, gastrin, expression of TGF-β and TNF-α, VIP and SP in small intestine.. The rats treated with reserpine, with similar signs to TCM spleen deficiency, show neuroendocrinoimmune disorders, and the restoration of the neuroendocrinoimmune disorders might be the part of mechanism of Lizhong Pill for reinforcing TCM spleen deficiency.

Topics: Animals; Atractylodes; Body Weight; China; Drugs, Chinese Herbal; Ethnopharmacology; Gastrins; Glycyrrhiza uralensis; Interferon-gamma; Interleukin-1; Interleukin-6; Intestine, Small; Male; Medicine, Chinese Traditional; Neuroimmunomodulation; Panax; Rats; Rats, Sprague-Dawley; Reserpine; Spleen; Substance P; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vasoactive Intestinal Peptide; Zingiber officinale

Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide with potent anti-inflammatory properties, and its receptor, VPAC1, mediates most of the anti-inflammatory effects of VIP. Diabetes mellitus is characterized by increased oxidation and inflammation due to persistent hyperglycemia. This research was performed to investigate the effects of VIP and a VPAC1 agonist on streptozotocin (STZ)-induced type 1 diabetic mice. Intraperitoneal injection of VIP and VPAC1 agonist (50nmol/kg/day in saline) over a 28-day period (1) decreased food intake, (2) increased body weight, (3) improved visceral index, (4) increased the fasting plasma insulin levels, (5) decreased the fasting plasma glucose, (6) improved the glucose tolerance, (7) decreased pancreas H(2)O(2) and malondialdehyde (MDA) and (8) increased total antioxidant activity (T-AOC) in the liver, spleen and pancreas. The results of histopathological and immunohistochemical analysis showed that VIP and the VPAC1 agonist improved the structure and cellularity of islets and ameliorated the insulin-secreting activity of islets. Additionally, administration of VIP or the VPAC1 agonist not only significantly decreased the plasma TNFα and CRP and promoted IL-10 in diabetic mice but also blocked the increased NF-κB activity of pancreatic tissue in diabetic mice. Furthermore, the VPAC1 agonist displayed stronger effects than VIP. These results show that both VIP and VPAC1 agonist ameliorated STZ-induced diabetes and protected mice against oxidative stress and inflammation associated diabetes, with VPAC1 being the receptor most responsible for these positive effects in diabetic mice.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes Mellitus, Experimental; Eating; Glucose Tolerance Test; Hydrogen Peroxide; Hypoglycemic Agents; Insulin; Interleukin-10; Liver; Male; Malondialdehyde; Mice; Mice, Inbred Strains; NF-kappa B; Pancreas; Peptide Fragments; Receptors, Vasoactive Intestinal Polypeptide, Type I; Spleen; Tumor Necrosis Factor-alpha; Vasoactive Intestinal Peptide

Distinct roles of the two T cell G protein-coupled receptors for vasoactive intestinal peptide (VIP), termed VPAC1 and VPAC2, in VIP regulation of autoimmune diseases were investigated in the dextran sodium sulfate (DSS)-induced murine acute colitis model for human inflammatory bowel diseases. In mice lacking VPAC2 (VPAC2-KO), DSS-induced colitis appeared more rapidly with greater weight loss and severe histopathology than in wild-type mice. In contrast, DSS-induced colitis in VPAC1-KO mice was milder than in wild-type mice and VPAC2-KO mice. Tissues affected by colitis showed significantly higher levels of myeloperoxidase, IL-6, IL-1β and MMP-9 in VPAC2-KO mice than wild-type mice, but there were no differences for IL-17, IFN-γ, IL-4, or CCR6. Suppression of VPAC1 signals in VPAC2-KO mice by PKA inhibitors reduced the clinical and histological severity of DSS-induced colitis, as well as tissue levels of IL-6, IL-1β and MMP-9. Thus VIP enhancement of the severity of DSS-induced colitis is mediated solely by VPAC1 receptors.

Topics: Animals; Body Weight; Colitis; Colon; Cyclic AMP-Dependent Protein Kinases; Dextran Sulfate; Disease Models, Animal; Female; Forkhead Transcription Factors; Gene Expression; Interleukin-17; Interleukin-1beta; Interleukin-6; Intestinal Mucosa; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Peroxidase; Protein Kinase Inhibitors; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Signal Transduction; T-Lymphocytes, Regulatory; Vasoactive Intestinal Peptide

The purpose of this work was to study the area of the varicosities of nerve fibers of myenteric neurons immunoreactive to vasoactive intestinal peptide (VIP-IR) and of the cell bodies of VIP-IR submucosal neurons of the jejunum of diabetic rats supplemented with 2% L-glutamine. Twenty male rats were divided into the following groups: normoglycemic (N), normoglycemic supplemented with L-glutamine (NG), diabetic (D) and diabetic supplemented with L-glutamine (DG). Whole-mounts of the muscle tunica and the submucosal layer were subjected to the immunohistochemical technique for neurotransmitter VIP identification. Morphometric analyses were carried out in 500 VIP-IR cell bodies of submucosal neurons and 2000 VIP-IR varicosities from each group. L-Glutamine supplementation to the normoglycemic animals caused an increase in the areas of the cell bodies (8.49%) and varicosities (21.3%) relative to the controls (P < 0.05). On the other hand, there was a decrease in the areas of the cell bodies (4.55%) and varicosities (28.9%) of group DG compared to those of group D (P < 0.05). It is concluded that L-glutamine supplementation was positive both to normoglycemic and diabetic animals.

Topics: Amino Acids, Essential; Animals; Antioxidants; Body Weight; Diabetes Mellitus, Experimental; Diet; Dietary Supplements; Enteric Nervous System; Fluorescent Antibody Technique, Indirect; Glutamine; Glycated Hemoglobin; Jejunum; Male; Myenteric Plexus; Neurons; Protective Agents; Rats; Rats, Wistar; Submucous Plexus; Vasoactive Intestinal Peptide

It is becoming apparent that there is a strong link between taste perception and energy homeostasis. Recent evidence implicates gut-related hormones in taste perception, including glucagon-like peptide 1 and vasoactive intestinal peptide (VIP). We used VIP knockout mice to investigate VIP's specific role in taste perception and connection to energy regulation.. Body weight, food intake, and plasma levels of multiple energy-regulating hormones were measured and pancreatic morphology was determined. In addition, the immunocytochemical profile of taste cells and gustatory behavior were examined in wild-type and VIP knockout mice.. VIP knockout mice demonstrate elevated plasma glucose, insulin, and leptin levels, with no islet beta-cell number/topography alteration. VIP and its receptors (VPAC1, VPAC2) were identified in type II taste cells of the taste bud, and VIP knockout mice exhibit enhanced taste preference to sweet tastants. VIP knockout mouse taste cells show a significant decrease in leptin receptor expression and elevated expression of glucagon-like peptide 1, which may explain sweet taste preference of VIP knockout mice.. This study suggests that the tongue can play a direct role in modulating energy intake to correct peripheral glycemic imbalances. In this way, we could view the tongue as a sensory mechanism that is bidirectionally regulated and thus forms a bridge between available foodstuffs and the intricate hormonal balance in the animal itself.

Topics: Animals; Blood Glucose; Blotting, Western; Body Weight; Eating; Glucagon-Like Peptide 1; Immunohistochemistry; Insulin; Leptin; Mice; Mice, Knockout; Receptors, Leptin; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Taste Buds; Vasoactive Intestinal Peptide

To evaluate the roles of enteric nervous system neurotransmitters, nitric oxide (NO), substance P (SP) and vasoactive intestinal polypeptide (VIP), and interstitial cells of Cajal (ICC) in the colon in slow transit constipation in rats.. Thirty-two healthy Wistar rats were randomly assigned to control and constipated groups. In the constipated group, the rats were daily administered with diphenoxylate (8 mg/kg) to develop slow transit constipation, while the control rats were fed with water. The number and the weight of fecal granule and the body weight of rats were recorded every 5 days for 90 days. Transit functions of intestinal movement were examined by an activated charcoal suspension pushing test one week after stopping the administration of diphenoxylate. The levels of NO and SP in the colonic mucosa were measured by nitrate reductase methods and ELISA respectively. The distribution of VIP and ICC positive cells confirmed with symbolic c-kit+ cells in the colonic wall were observed by immunohistochemical methods.. The daily number of fecal granule in the constipated group was significantly less than that in the control group (P<0.01). The mean weight of each fecal granule in the constipated group was significantly higher than that in the control group (P<0.01). The discharge time of the first granule of black faeces in the constipated group (430.2+/- 132.1 min) was significantly longer than that in the control group (337.2+/- 74.7 min; P<0.05). There were no significant differences in NO and SP levels and the density of VIP positive cells in the distal colonic segment between the two groups. The number of c-kit+ cells in the distal colonic wall in the constipated group was significantly reduced compared with that in the control group (P<0.05).. The reduction of ICC number in the distal colon may be contributed to the pathogenesis of slow transit constipation in rats.

Topics: Animals; Body Weight; Coiled Bodies; Colon; Constipation; Male; Neurotransmitter Agents; Nitric Oxide; Proto-Oncogene Proteins c-kit; Rats; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide

It was hypothesized that the VPAC1 agonist may exert anti-obesity functions because VPAC1 is involved in the anorexigenic effects and the anti-inflammatory function of pituitary adenylate cyclase-activating polypeptide (PACAP)/vasoactive intestinal polypeptide (VIP). Furthermore, our in vitro test showed that the expression of VPAC1 increased significantly after the 3T3-L1 adipocytes were differentiated, and that incubation of adipocytes with VPAC1 agonist (10-1 000 nmol/L per 1x10(6) cells) resulted in stimulation of lipolysis. To test the effect of VPAC1 agonist [Lys15, Arg16, Leu27]-VIP (1-7) GRF (8-27) on diet-induced obesity (DIO), we further designed the following two in vivo experiments: (1) Mice were fed on high-fat diet (HFD) and intraperitoneally (i.p.) treated with VPAC1 agonist simultaneously for 28 d; (2) Mice were given HFD for 35 d, and subsequently fed on the same HFD and i.p. treated with VPAC1 agonist for the next 28 d. The physiological indices, including body weight, weight of white adipose tissue, plasma glucose and blood lipid, were collected. The results showed that treatment with VPAC1 agonist inhibited ingestion significantly and prevented the elevations in body weight and the weights of the white adipose tissues (epididymal and dorsal) induced by HFD. The increases in plasma glucose, cholesterol, triglycerides and LDL induced by HFD were also down-regulated in mice treated with VPAC1 agonist. VPAC1 agonist treatment also improved the glucose tolerance. Therefore, VPAC1 agonist treatment inhibits the development of the obesity induced by HFD and helps to improve the morbidities associated with DIO.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Body Weight; Diet, High-Fat; Mice; Obesity; Receptors, Vasoactive Intestinal Polypeptide, Type I; Vasoactive Intestinal Peptide

Pharmacological studies indicate that vasoactive intestinal peptide (VIP) may be necessary for normal embryonic development in the mouse. For example, VIP antagonist treatment before embryonic day 11 resulted in developmental delays, growth restriction, modified adult brain chemistry and reduced social behavior. Here, developmental milestones, growth, and social behaviors of neonates of VIP-deficient mothers (VIP +/-) mated to VIP +/- males were compared with the offspring of wild type mothers (VIP +/+) mated to VIP +/+ and +/- males, to assess the contributions of both maternal and offspring VIP genotype. Regardless of their own genotype, all offsprings of VIP-deficient mothers exhibited developmental delays. No delays were seen in the offspring of wild type mothers, regardless of their own genotype. Body weights were significantly reduced in offspring of VIP-deficient mothers, with VIP null (-/-) the most affected. Regardless of genotype, all offspring of VIP-deficient mothers expressed reduced maternal affiliation compared with wild type offspring of wild type mothers; +/- offspring of wild type mothers did not differ in maternal affiliation from their wild type littermates. Play behavior was significantly reduced in all offsprings of VIP-deficient mothers. Maternal behavior did not differ between wild type and VIP-deficient mothers, and cross-fostering of litters did not change offspring development, indicating that offspring deficits were induced prenatally. This study illustrated that the VIP status of a pregnant mouse had a greater influence on the growth, development and behavior of her offspring than the VIP genotype of the offspring themselves. Deficiencies were apparent in +/+, +/- and -/- offspring born to VIP-deficient mothers; no deficiencies were apparent in +/- offspring born to normal mothers. These results underscore the significant contribution of the uterine environment to normal development and indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders with social behavior deficits such as autism.

Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Female; Genotype; Male; Mice; Mice, Knockout; Social Behavior; Vasoactive Intestinal Peptide

In the present study we evaluated the effects of early social isolation and re-socialization on dendritic development and the expression of the vasoactive intestinal peptide (VIP) in the medial prefrontal cortex (mPFC) of the rat. Sprague-Dawley male rats were reared either in isolation (IC) or social (SC) conditions from postnatal day 18 to 32. Rats were then behaviorally evaluated in the open field test, and approximately half of the animals were sacrificed. Their brains were processed either for immunocytochemical labeling against VIP or for the Golgi-Cox-Sholl staining. The remaining IC rats were re-socialized during 30 additional days. The results demonstrated that early social isolation impair neuronal dendritic arborization and increase the number of VIP-immunoreactive neurons. Furthermore, animals displayed hyperlocomotion in the open-field test. According to our structural, immunocytochemical and open-field data, the resocialization experience was unable to reverse neuronal and behavioral abnormalities.

Topics: Age Factors; Animals; Animals, Newborn; Behavior, Animal; Body Weight; Cell Count; Dendrites; Gene Expression Regulation, Developmental; Immunohistochemistry; Male; Motor Activity; Neurons; Prefrontal Cortex; Random Allocation; Rats; Rats, Sprague-Dawley; Social Isolation; Socialization; Vasoactive Intestinal Peptide

In mammals, the main circadian pacemaker is located in the suprachiasmatic nucleus (SCN) and its most potent synchronizer is the daily variation of the intensity of light. However, other nonphotic cues, such as timed food restriction, can induce changes in the circadian rhythms, leading also to the appearance of a food-entrained oscillator. The present study was designed to establish if the alterations of the circadian rhythms induced by timed hypocaloric food restriction are accompanied by structural changes in the SCN. Two groups of adult rats, both maintained on 12-h light/12-h dark cycles, were used; in one group, animals had permanent free access to food, whereas in the other they were subjected to a restricted hypocaloric early morning feeding during 7 months. Using stereological techniques and in situ hybridization, we have examined the structure of the SCN and the synthesis and expression of vasopressin (AVP) and vasoactive intestinal peptide (VIP). The volume of the SCN and the total number of neurons did not vary between the two groups. However, the total number of AVP- and VIP-immunoreactive neurons and the AVP and VIP mRNA levels were significantly decreased in timed hypocaloric food-restricted animals. The results indicate that timed hypocaloric food restriction has led to changes of AVP and VIP content of the neurons. They furthermore suggest the existence of a coupling between the food-entrainable oscillator and the light-entrainable pacemaker.

Topics: Animals; Arginine Vasopressin; Body Weight; Cell Count; Circadian Rhythm; Food Deprivation; Gene Expression Regulation; Immunohistochemistry; In Situ Hybridization; Male; Neurons; Organ Size; Rats; Rats, Wistar; RNA, Messenger; Suprachiasmatic Nucleus; Time Factors; Vasoactive Intestinal Peptide

Assessment of seasonal variations in expression of brain neuropeptide mRNA is complicated by concurrent circadian variations. Because entrainment of suprachiasmatic nucleus (SCN) based rhythms differs in long versus short day lengths, valid seasonal comparisons must be made at equivalent circadian phases. We used a novel experimental design which permitted sampling at identical circadian phases of animals exhibiting opposite seasonal reproductive responses to the same intermediate day length. This allowed us to test whether seasonal changes in arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) mRNA expression in the SCN occur in the absence of the pineal gland. Juvenile Siberian hamsters were gestated and maintained postnatally in either a long photoperiod (16 h light/day) or short photoperiod (10 h light/day). At the time of weaning (18 days of age), the hamsters were pinealectomized and either transferred to a new photoperiod (10-, 16- or 14-h light/day) or left in the original photoperiod. Hamsters from 10L had substantially smaller and lighter testes than those from 16L. If photoperiodic modulation of AVP and VIP mRNA expression occurs in the absence of the pineal, then transfer of pinealectomized hamsters from a longer (16L) or shorter (10L) photoperiod to an intermediate photoperiod (14L) should result in a differential response with respect to SCN AVP and VIP mRNA expression but not testis size. When sampled at an identical circadian phase (3 h after lights on) in 14L there was no difference in the expression of AVP or VIP mRNA in the SCN between animals previously housed in long versus short day lengths. In contrast to a previous study that did not carefully control for circadian phase, the present findings suggest that seasonal photoperiodic control of SCN neuropeptide mRNA expression depends upon the pineal gland. In addition, the present findings demonstrate a significant, negative correlation between AVP mRNA expression in the SCN and the length of the daily active phase (alpha).

Topics: Animals; Animals, Newborn; Arginine Vasopressin; Body Weight; Circadian Rhythm; Cricetinae; Female; Gene Expression Regulation; Male; Melatonin; Motor Activity; Neurons; Organ Size; Phodopus; Photoperiod; Pineal Gland; RNA, Messenger; Seasons; Suprachiasmatic Nucleus; Testis; Vasoactive Intestinal Peptide

Topics: Animals; Body Weight; Disaccharidases; Dogs; Gastrointestinal Hormones; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Models, Animal; Organ Size; Reference Values; Serotonin; Substance P; Transplantation, Autologous; Vasoactive Intestinal Peptide; Xylose

The exocrine pancreas of the cystic fibrosis (CF) mouse (cftr(m1UNC)) is only mildly affected compared with the human disease, providing a useful model to study alterations in exocrine function. The CF mouse pancreas has approximately 50% of normal amylase levels and approximately 200% normal Muclin levels, the major sulfated glycoprotein of the pancreas. Protein biosynthetic rates and mRNA levels for amylase were not altered in CF compared with normal mice, and increases in Muclin biosynthesis and mRNA paralleled the increased protein content. Stimulated pancreatic amylase secretion in vitro and in vivo tended to be increased in CF mice but was not statistically significant compared with normal mice. We show for the first time that the CF mouse duodenum is abnormally acidic (normal intestinal pH = 6.47 +/- 0.05; CF intestinal pH = 6.15 +/- 0.07) and hypothesize that this may result in increased signaling to the exocrine pancreas. There were significant increases in CF intestinal mRNA levels for secretin (310% of normal, P < 0.001) and vasoactive intestinal peptide (148% of normal, P < 0.05). Furthermore, CF pancreatic cAMP levels were 147% of normal (P < 0.01). These data suggest that the CF pancreas may be chronically stimulated by cAMP-mediated signals, which in turn may exacerbate protein plugging in the acinar/ductal lumen, believed to be the primary cause of destruction of the pancreas in CF.

Topics: Amylases; Animals; Body Weight; Calcium-Binding Proteins; Cyclic AMP; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA-Binding Proteins; Humans; Immunohistochemistry; Intestine, Small; Mice; Mice, Inbred CFTR; Mucins; Pancreas; Secretin; Tumor Suppressor Proteins; Vasoactive Intestinal Peptide

The importance of late winter pairing activity on the neuroendocrinology of wild waterfowl is unknown. In this study, we examined the sex-related differences in the roles of late winter pairing activity and seasonal influences on neuroendocrine and reproductive physiology in both male and female mallards. Our main goals were to determine (1) which physiological responses were influenced by pairing status or by seasonal changes and (2) whether responses differed between the sexes. Thus, physiological responses of mallards in different pairing status categories were assessed at two times: January 28 to February 5 and February 24 to March 3. Ducks were assigned to one of the following pairing status categories: strong pairs, temporary pairs, unpaired or lone birds within the flock, or birds isolated in same-sex groups. Seasonal changes correlated with increases in both gonadal mass and hypothalamic content of vasoactive intestinal peptide in both sexes, whereas only pairing status correlated with changes in body mass in both sexes. The main sex-related differences were the following: (1) Seasonal decreases in hypothalamic gonadotrophin releasing hormone II content occurred only in females. (2) Seasonal increases in serum prolactin occurred only in males, whereas levels in females were low throughout the study. (3) Both male and female gonadal masses increased seasonally, but male gonadal mass was initially twice that of females. (4) Body mass of both sexes was influenced by pairing status correlations (i.e., all paired or lone birds were heavier than isolated birds), but body mass in males decreased seasonally. No sex-related differences occurred in hypothalamic gonadotrophin releasing hormone I content or circulating serum luteinizing hormone. Taken together, these results indicate that seasonal reproduction in mallards is regulated not only by seasonal but also by social cues, and differences occur between the sexes, months in advance of actual breeding.

Topics: Animals; Body Weight; Female; Gonadotropin-Releasing Hormone; Gonads; Hypothalamus; Luteinizing Hormone; Male; Neurosecretory Systems; Prolactin; Pyrrolidonecarboxylic Acid; Reproduction; Seasons; Sex Characteristics; Sexual Behavior, Animal; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) and calcitonin gene-related peptide (CGRP)-LI concentrations were determined in the developing rat heart atria using radioimmunoassay. Peptide levels were analysed on postnatal days 1, 10, 25, 45, 60, and 85 (P1-P85) separately in the right (RA) and left atria (LA). No sex differences were revealed at any age examined. VIP-LI has been already detected in both atria at P1 in concentrations comparable to values at P10. In the RA, VIP-LI levels increased significantly between days P10 and P25, remained high at P45 and then declined. In the LA, VIP-LI concentrations did not differ from those in the RA on days P1, P10, P25, and P45. However, regional differences were found at P60 and P85, when the peptide levels were significantly higher in the LA than in the RA. The postnatal changes in CGRP-LI concentrations were comparable in both atria with similar values at P1 and P85. After birth, CGRP levels decreased gradually till P45, then they increased till P60 and declined again at P85. The results demonstrate that there is an asymmetry in the postnatal development of the atrial VIP-LI and CGRP-LI concentrations. VIP-LI levels reached their maximum at P25, whereas CGRP-LI levels at P60. Relatively high peptide concentrations in neonatal atria and their variations during development might be related to diverse trophic functions of VIP and CGRP.

Topics: Animals; Autonomic Pathways; Body Weight; Calcitonin Gene-Related Peptide; Heart Atria; Organ Size; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

The islet response to a high-fat diet, which induces insulin resistance, was investigated in Sprague-Dawley rats. It was found that the insulin response to glucose (15 or 25 mg/min, i.v.) was not different between rats given a high-fat diet and control rats after 2 weeks but was significantly reduced in rats fed high-fat diets after 4 (by 46+/-9%; p<0.001) and 8 weeks (by 68+/-12%; p<0.001). However, after 2 weeks of a high-fat diet, stimulated insulin secretion from isolated islets incubated for 60 min in 5.6, 8.3, and 11.1 mM glucose was impaired. When islets isolated from rats given a high-fat diet for 2 weeks were perifused, it was evident that the first-phase insulin secretion was impaired (seen during the first 6 min after increase of glucose from 3.3 to 8.3 mM). Insulin gene expression, examined by quantitative in situ hybridization, was impaired after 2 weeks of high-fat diet (52% decrease in mRNA-labeling; p<0.001). Islet hypertrophy was not evident in rats given high-fat diet, as determined by areas of either islet profiles in dark-field images or isolated islets. Islet innervation, as revealed by immunostaining for vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), was increased after 2, 4, and 8 weeks of high-fat diet. Thus induction of insulin resistance by high-fat diet in Sprague-Dawley rats results after 2 weeks in impaired glucose-stimulated insulin secretion in vitro, impaired insulin gene expression, and hyperinnervation of the islets without any sign of islet hypertrophy, whereas the in vivo insulin response to glucose, although normal after 2 weeks, is impaired after 4 weeks.

Topics: Animals; Blood Glucose; Body Weight; Cells, Cultured; Dietary Fats; Female; Gene Expression Regulation; Glucose; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Neuropeptide Y; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors; Transcription, Genetic; Triglycerides; Vasoactive Intestinal Peptide

Pituitary adenylate cyclase activating polypeptide (PACAP), which was isolated from ovine hypothalamic extract, has been shown to have a physiological role in the regulation of insulin or islet functions. In streptozotocin (STZ)-induced diabetic rats, we examined the content of PACAP immunoreactivity and gene expression of three specific receptors. Four weeks after administration of STZ (50 mg/kg), plasma glucose levels increased 3.3-fold, and plasma insulin levels decreased to one-tenth as compared with the control. The content of PACAP immunoreactivity in the pancreas potently increased by 30%, but the content of vasoactive intestinal polypeptide (VIP) immunoreactivity was not changed. In the other tissues, the content of PACAP immunoreactivity did not significantly change except in the hypothalamus, which showed a 10% increment. In the expression level of PACAP/VIP receptors, semi-quantitative RT-PCR analysis revealed that VIP1/PACAP receptor mRNA significantly increased as compared with the other two types of receptors in the pancreas of STZ-induced diabetic rats. These findings suggest that PACAP and VIP1/PACAP receptor might be involved in the pathophysiology of diabetes mellitus.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Hypothalamus; Insulin; Male; Neuropeptides; Pancreas; Pituitary Adenylate Cyclase-Activating Polypeptide; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; RNA, Messenger; Streptozocin; Vasoactive Intestinal Peptide

To study islet function following reduced insulin sensitivity, we examined mice of the C57BL/6J strain, the genotype of which carries an increased propensity to develop insulin resistance when metabolically challenged. The mice received either a high-fat diet (58% fat on an energy basis) or a control diet (11% fat) for 12 weeks. The body weight of mice on the high-fat diet increased significantly more than that of mice on the control diet (25.8 +/- 0.4 v 21.3 +/- 0.2 g, P < .001). Already after 1 week on the high-fat diet, a significant hyperglycemia accompanied by hyperinsulinemia had evolved, indicative of insulin resistance. After 12 weeks, plasma glucose levels for high-fat diet-treated mice were 7.5 +/- 0.1 mmol/L, versus 6.5 +/- 0.1 mmol/L in controls (P < .001); corresponding values for plasma insulin were 248 +/- 17 and 104 +/- 7 pmol/L, respectively (P < .001). Mice given a high-fat diet also had elevated levels of total cholesterol, triglycerides, and free fatty acids (FFAs) compared with controls. After 4, 8, and 12 weeks, glucose (2.8, 8.3, or 16.7 mmol/kg) or the cholinergic agonist carbachol (0.16 or 0.53 micromol/kg) was injected intraperitoneally. The insulinotropic response to glucose was not different between the two groups after 4 or 8 weeks, whereas after 12 weeks, glucose-induced insulin secretion was markedly impaired in high-fat diet-treated mice (P < .001). In contrast, after 8 and 12 weeks on a high-fat diet, carbachol-stimulated insulin secretion was potentiated (P < .01), whereas carbachol-stimulated glucagon secretion was not significantly altered. Furthermore, after 12 weeks on the high-fat diet, insulin secretion from isolated islets was impaired at glucose levels of 8.3, 11.1, and 16.7 mmol/L (P < or = .05). Moreover, islet morphology as examined by immunocytochemistry using insulin antibodies and islet innervation, as revealed by immunostaining of tyrosine hydroxylase (TH), neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP), and substance P (SP) were unaffected by the high-fat diet for 12 weeks. However, quantitative in situ hybridization showed a 3.5-fold upregulation of insulin gene expression in response to the high-fat diet (P < .001) despite unaltered B-cell mass and pancreatic insulin content. We conclude that as little as 1 week of treatment with a high-fat diet induces insulin resistance in C57BL/6J mice. This is accompanied later by hyperlipemia, potentiated carbachol-stimulated insulin secretio

Topics: Animals; Blood Glucose; Body Weight; Carbachol; Cholesterol; Dietary Fats; Eating; Fatty Acids, Nonesterified; Female; Fluorescent Antibody Technique, Indirect; Galanin; Gene Expression; Genotype; Glucagon; Glucose; Immunohistochemistry; In Situ Hybridization; Insulin; Insulin Resistance; Islets of Langerhans; Mice; Mice, Inbred C57BL; Muscarinic Agonists; Neuropeptide Y; Substance P; Triglycerides; Vasoactive Intestinal Peptide

Previous work has shown that blockade of VIP function in the early postimplantation embryo results in growth retardation and microcephaly. In the present work, the neurobehavioral development of neonatal mice was examined following treatment of dams with a VIP antagonist during this period. Inhibition of VIP functions during early embryogenesis impaired the performance of 5 of 10 developmental behaviors. These behaviors included developmental milestones (first appearance of ear twitch and eye opening) and complex motor behaviors (negative geotaxis, surface righting, and air righting). The retardation of neurobehavioral development produced by inhibition of VIP action indicates that this peptide is important to the progression of embryonic development.

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Embryonic and Fetal Development; Embryonic Development; Female; Growth Inhibitors; Mice; Motor Activity; Neurotensin; Pregnancy; Recombinant Fusion Proteins; Vasoactive Intestinal Peptide

The aim of the study was to evaluate the effects of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) on splanchnic blood flow in anesthetized rats. For this purpose, either PACAP-38 dissolved in saline or saline alone was injected intravenously 5 (10 nmol/kg body weight (bw) PACAP-38) and 30 min (5 or 10 nmol/kg) before measurements. The blood flow to the whole pancreas, islets, duodenum and colon was then measured with a microsphere technique. The higher dose of PACAP-38 slightly increased blood glucose concentrations at both 5 and 30 min after administration, whereas the lower had no effect. Both doses of PACAP-38 induced a transient initial decrease in mean arterial blood pressure. The lower dose of PACAP-38 decreased fractional islet blood flow 30 min after administration, but did not affect the other blood flows. The higher dose of the peptide (10 nmol/kg bw) caused an increase in whole pancreatic blood flow at both 5 and 30 min after administration, whereas islet blood flow was only increased at the former time. At both time points PACAP-38 redistributed the blood flow within the pancreas in favour of the exocrine pancreas. This resulted in a decreased fractional islet blood flow, i.e., the fraction of whole pancreatic blood flow diverted through the islets. At 5 min after PACAP-38 administration duodenal blood flow was decreased, whereas after 30 min no effects on duodenal or colonic blood flow were observed. Administration of a VIP antagonist intravenously (20 nmol/kg bw) decreased the PACAP-38-induced pancreatic blood flow increase and intrapancreatic redistribution. When only the VIP antagonist was given both pancreatic and islet blood decreased in concert. It is concluded that administration of PACAP-38 induces a blood flow increase in the pancreas, preferably in the exocrine parts of the gland, by actions mediated by PACAP-38 receptors shared with VIP.

Topics: Amino Acid Sequence; Animals; Blood Circulation; Blood Glucose; Blood Pressure; Body Weight; Male; Molecular Sequence Data; Neuropeptides; Pancreas; Peptides; Pituitary Adenylate Cyclase-Activating Polypeptide; Pituitary Gland; Rats; Rats, Sprague-Dawley; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide; Vasodilator Agents

Rats previously starved for 30 h were offered hard chow over a period of 80 min, and the effect of eating on the parotid gland content of vasoactive intestinal peptide (VIP), substance P and neuropeptide Y (NPY) was examined. In rats pretreated with I.P. atropine and alpha- and beta-adrenoceptor blocking agents, the total amounts of VIP and substance P were reduced after feeding by 23 and 42%, respectively; in contrast the NPY content was not significantly affected. Similarly, in animals given atropine alone the VIP content was reduced by 25% and substance P by 40% after feeding. In the absence of autonomic receptor blockade, there was no loss of parotid neuropeptide content in response to feeding. Neither an intact sympathetic innervation nor a capsaicin-sensitive sensory innervation was a prerequisite for depletion of parotid neuropeptides in the presence of atropine and adrenoceptor blockers. The observed decrease in neuropeptide content is thought to reflect an imbalance between peptide release from nerve terminals and their replenishment by axonal transport, this imbalance resulting from the unusually high demands on the parasympathetic non-adrenergic, non-cholinergic (NANC) mechanism. Under normal conditions salivary peptidergic mechanisms are spared as seen in the absence of autonomic receptor blockade.

Topics: Adrenergic Antagonists; Animals; Atropine; Body Weight; Capsaicin; Diet; Female; Neuropeptide Y; Organ Size; Parotid Gland; Phentolamine; Propranolol; Rats; Rats, Sprague-Dawley; Reflex; Substance P; Sympathectomy; Vasoactive Intestinal Peptide

We have recently reported that hypothyroidism increases immunoreactive (IR)-vasoactive intestinal polypeptide (VIP) and VIP mRNA content in both parvocellular and magnocellular neurons of the rat, hypothalamic paraventricular nucleus (PVN). As VIP can stimulate vasopressin (AVP) secretion, we conducted an anatomical investigation to determine whether VIP-containing neurons in other regions of the brain that are involved with homeostatic mechanisms of water and salt conservation are also affected by hypothyroidism. The distribution and intensity of VIP immunostaining in neurons and fibers of the magnocellular-neurohypophysial system, including the hypothalamic PVN, supraoptic nucleus (SON) and accessory magnocellular cell groups, circumventricular subfornical organ (SFO), preoptic and anterior hypothalamus, midline thalamus, subthalamic zona incerta and posterior septal nuclei were studied using a highly sensitive immunocytochemical technique and unbiased neuronal counting methods, based on the optical dissector principle. Hypothyroidism increased the intensity of VIP immunostaining and/or the number/section, percentage and numerical density of IR-VIP neurons in the PVN, SON, nucleus circularis, periventricular preoptic nucleus of the hypothalamus and SFO. In addition, IR-VIP perikarya and/or fibers in the hypothalamic medial preoptic area and anterior periventricular nucleus, nucleus reuniens of the thalamus and dorsal fornix-triangular septal nucleus complex were also apparent in the hypothyroid animals while no immunostaining was seen in these areas in control animals. No quantitative and/or qualitative modifications in IR-VIP neurons and fibers were noted in the anterior hypothalamic area, suprachiasmatic nucleus, thalamic paraventricular nucles an subthalamic zona incerta between hypothyroid and control animals. These findings suggest an inverse relationship between thyroid hormone and VIP content and/or distribution of IR-VIP neurons in specific forebrain regions involved in the control of AVP release, extracellular fluid volume, thirst, blood pressure and anterior pituitary secretion. This raises the possibility that changes in fluid homeostasis and cardiovascular function occurring in hypothyroidism may be mediated, at least in part, by VIP-producing neurons in diverse regions of the brain.

Topics: Animals; Antithyroid Agents; Body Weight; Hypothyroidism; Immunohistochemistry; Male; Methimazole; Nerve Fibers; Neurons; Pituitary Gland, Posterior; Prosencephalon; Rats; Rats, Sprague-Dawley; Thyroid Hormones; Vasoactive Intestinal Peptide

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

This study was designed to assess the effects of experimental diabetes and nerve crush injury upon vasoactive intestinal polypeptide (VIP) content and axonal transport in the dorsal root ganglia (DRG) and sciatic nerve. Sciatic nerve crush injury in control and 3-week streptozotocin-diabetic rats was followed 6.5 days later by placement of 2 constricting ligatures above the site of injury. After 12 h, the L4 and L5 DRG and sciatic nerve were removed for VIP radioimmunoassay. Similar samples were also taken from control and diabetic rats whose nerve had been ligated without a preceding crush. VIP was increased over 2-fold in ganglia and 4-fold in nerves of crush-injured controls compared to uninjured controls (both P < 0.01). Crush injury also increased ganglion and nerve VIP in diabetic rats (P < 0.05 and 0.01, respectively) but the increase was less than what occurred in crush-injured controls (both P < 0.05). The accumulation of VIP proximal to a sciatic ligature was similar in control and diabetic rats and was not altered in either group by crush injury, while retrograde transport of VIP was initiated by crush injury in both control and diabetic rats. These data show that short-term diabetes does not alter the amount and peripheral axonal transport of VIP in the sciatic nerve but impairs the ability of peripheral nerve to respond to injury.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Ganglia, Spinal; Male; Nerve Crush; Nerve Regeneration; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Vasoactive Intestinal Peptide

VIP is widely distributed in the body, and among others is present within the hypothalamo-pituitary-adrenal axis. The aim of this study was to investigate the effect of prolonged VIP administration on the structure and function of the rat adrenal cortex. Adult female rats were treated for 7 or 14 days with VIP (1.5 micrograms/100 g/day). This treatment did not change adrenal weight and evoked only slight changes in the stereologic parameters of adrenal cortex (volume of adrenocortical zones, average cell volume and number of cells in the gland). On the contrary, basal plasma corticosterone levels were markedly lowered (44% and 26% of control values in 7- and 14-day experiments, respectively), an effect accompanied by a significant decrease in corticosterone output by adrenal slices. After standardized ether stress, blood corticosterone concentration was similar in control and 14-day VIP-treated rats, while corticosterone secretion by adrenal quarters was higher in VIP-administered animals. Thus, prolonged VIP administration results in an unusual inhibition of corticosterone secretion in the rat, which is not coupled with a compensatory hypertrophy of the rat adrenal cortex. Such changes may depend on a modulatory action of VIP on the hypothalamo-pituitary-adrenal axis, and its possible mechanism is discussed.

Topics: Adrenal Cortex; Animals; Body Weight; Corticosterone; Ether; Female; In Vitro Techniques; Organ Size; Pituitary Gland, Anterior; Rats; Rats, Wistar; Stress, Physiological; Time Factors; Vasoactive Intestinal Peptide

The effect of streptozotocin-induced diabetes on the production of vasoactive intestinal polypeptide messenger RNA in the myenteric neurones of 8 weeks diabetic rat intestine was examined using in situ hybridization. Total ganglion cell number per length (mm) of tissue section was measured using NADH diaphorase histochemistry. Although ganglion cells were more numerous in the control preparations compared with diabetic samples, a significantly greater number of vasoactive intestinal polypeptide messenger RNA-containing cells was detected in the diabetic tissues. These observations suggest that there is either a decrease in the breakdown of vasoactive intestinal polypeptide messenger RNA or an increase in its synthesis in myenteric neurones of diabetic rat intestine.

Topics: Animals; Body Weight; Diabetes Mellitus, Experimental; Ganglia; Histocytochemistry; In Situ Hybridization; Male; Myenteric Plexus; NADPH Dehydrogenase; Neurons; Protein Biosynthesis; Rats; Rats, Wistar; RNA, Messenger; Vasoactive Intestinal Peptide

The contractile effect of methacholine, prostaglandin F2 alpha (PGF2 alpha) and electrical stimulation of cholinergic neurones, and the relaxant effect of nitric oxide (NO), vasoactive intestinal polypeptide (VIP) and electrical stimulation of inhibitory non-adrenergic non-cholinergic (NANC) neurones were studied in longitudinal smooth muscle strips of the gastric fundus of young (3 months), adult (12 months) and old (24 months) male Wistar rats. The contractile responses to methacholine and to electrical stimulation of cholinergic neurones were not significantly different between the three age groups. The responses to PGF2 alpha were significantly more pronounced in young than in adult and old rats. The relaxant response to electrical stimulation of NANC neurones with a cumulative increase in frequency showed a decreased response in old rats at the higher stimulation frequencies. This was mimicked by a decreased response to VIP, suggesting that there is a decrease in muscular sensitivity to VIP rather than an impaired capacity to VIP release with increasing age. The relaxant response to electrical stimulation of NANC neurones with short trains was similar in the three age groups, while the sensitivity to exogenous NO increased with age. The latter might be a compensatory mechanism for a decrease in stimulation-induced NO release with age.

Topics: Aging; Animals; Autonomic Nervous System; Body Weight; Dinoprost; Electric Stimulation; Gastric Fundus; Male; Methacholine Compounds; Muscle Contraction; Muscle, Smooth; Neurons; Nitric Oxide; Organ Size; Parasympathetic Nervous System; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

Vasomotor responses of isolated coronary arteries to peptide and nonpeptide neurotransmitter agents changed with the development of sexual maturity in female New Zealand white rabbits aged 4-12 months. There was a significant reduction from 4- to 12-month-old animals in both the direct smooth muscle vasodilator responses to calcitonin gene-related peptide (p less than 0.01) and vasoactive intestinal polypeptide (p less than 0.001), and in the endothelium-mediated response to substance P (p less than 0.005). Vasodilator responses to concentrations of acetylcholine (ACh) greater than 0.1 microM were virtually absent in the 6- and 12-month-old animals. No change in maximal relaxation to noradrenaline was seen with maturation, although there was a small significant increase in potency. The contractile response of the smooth muscle to 30 mM KCl declined steadily as the animals matured, but the maximal contraction to ACh (p less than 0.05), neuropeptide Y (p less than 0.02), and serotonin (p less than 0.05) increased significantly between 4 and 12 months of age. These results indicate that following sexual maturation in the female rabbit, the epicardial coronary artery shows a significant increase in maximum responses to vasoconstrictor neurotransmitter agents and, at the same time, a marked decline in responses to some vasodilator agents, both those acting directly on the smooth muscle and those acting via the endothelium.

Topics: Acetylcholine; Aging; Animals; Body Weight; Calcitonin Gene-Related Peptide; Coronary Vessels; Female; In Vitro Techniques; Muscle Contraction; Muscle, Smooth, Vascular; Neuropeptide Y; Neurotransmitter Agents; Norepinephrine; Potassium Chloride; Rabbits; Serotonin; Sexual Maturation; Substance P; Vasoactive Intestinal Peptide

The effects of lesions of the suprachiasmatic (SCN) and paraventricular nuclei (PVN) of the hypothalamus on photoperiodic responses were examined in adult Siberian hamsters. SCN lesions reduced nocturnal water intake in long days, whereas PVN lesions increased body weight and food intake in both short and long days. SCN or PVN lesions blocked short-day-induced decreases in body, fat pad, and testes weights and in food intake. Serum prolactin (PRL), but not follicle-stimulating hormone, levels were increased. The distribution of immunostained neurons and fibers for gonadotropin-releasing hormone (GnRH), beta-endorphin, arginine vasopressin (AVP), and vasoactive intestinal polypeptide (VIP) resembled that of other rodent species. Short-day exposure reduced AVP staining in lateral septum, medial amygdala, and bed nucleus of the stria terminalis but not in the PVN of the thalamus or the SCN. Short-day-exposed hamsters had fewer beta-endorphin-positive arcuate nucleus cells and tended to have fewer GnRH-positive preoptic cells than long-day controls. VIP staining was unaffected by photoperiod. Most day length effects on immunostaining were eliminated by either lesion. These results establish the importance of the SCN and PVN in the photoperiodic control of several seasonal responses in Siberian hamsters.

Topics: Analysis of Variance; Animals; Arginine Vasopressin; beta-Endorphin; Body Weight; Brain Diseases; Circadian Rhythm; Cricetinae; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Immunohistochemistry; Luteinizing Hormone; Male; Melatonin; Neuropeptides; Paraventricular Hypothalamic Nucleus; Prolactin; Suprachiasmatic Nucleus; Testis; Vasoactive Intestinal Peptide

After induction of diabetes with streptozocin (STZ-D) in rats, we measured vasoactive intestinal polypeptide (VIP) content in sciatic nerve and spinal cord obtained from nondiabetic, untreated STZ-D, and insulin-treated STZ-D rats. Eight weeks after the onset of diabetes, caudal nerve conduction velocity (NCV) in the untreated STZ-D rats (n = 13) was slower than in the controls (n = 11; mean +/- SE 30.9 +/- 0.6 vs. 41.4 +/- 1.8 m/s, P less than 0.001). The decrease in NCV was less marked in the insulin-treated STZ-D rats (n = 11; 36.3 +/- 0.9 m/s, P less than 0.05 vs. control). VIP content in sciatic nerve decreased in the untreated STZ-D rats (1.33 +/- 0.23 ng/g wet wt) compared with the other groups (control, 3.10 +/- 0.44, P less than 0.01; insulin-treated STZ-D, 2.44 +/- 0.55, P less than 0.05). However, in spinal cord, VIP content was not significantly different among the three groups. The VIP levels in sciatic nerve showed a positive correlation with NCV (r = 0.430, P less than 0.01). In addition, an inverse correlation between VIP levels and blood glucose levels was observed (r = -0.5624, P less than 0.001). NCV was also inversely correlated with blood glucose levels (r = -0.7662, P less than 0.001). Together with a previous morphological study, these findings suggest a possible causal relationship between reduced VIP content and diabetic neuropathy.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Insulin; Male; Neural Conduction; Radioimmunoassay; Rats; Rats, Inbred Strains; Sciatic Nerve; Spinal Cord; Vasoactive Intestinal Peptide

The rat has been a useful model for studying neuronal and metabolic abnormalities associated with fetal and neonatal hypothyroidism produced by treatment of the mother with antithyroid medication. The neonates are then maintained on this medication via the mother's milk until weaning and subsequently through the drinking water. We have determined the concentrations and contents of immunoreactive cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the brain and gut of groups of rats exposed to antithyroid medication from day 16 of gestation. The neonates were sacrificed at 2, 4, 8 and 12 weeks. Compared to controls total body weight was greatly reduced in methimazole (MMI)-treated rats, all of whom were hypothyroid as evidenced by marked reduction of T4 and increase in TSH. Discontinuation of MMI-treatment after 8 weeks resulted in normalization of T4 and TSH and a dramatic weight gain but at 12 weeks the brain weights of the MMI-treated rats were reduced by 17% and the brain contents, of CCK and VIP were similarly reduced. Tissue weights throughout the gut were 1/2 or less than those of control rats. Since VIP but not CCK concentrations in the gut of MMI-treated animals were significantly greater than those of the control animals, it would appear that there was greater loss of mucosal tissue with its endocrine content of CCK than of neuronal tissue with its greater content of VIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Animals, Newborn; Body Weight; Brain Chemistry; Cholecystokinin; Digestive System; Female; Hypothyroidism; Methimazole; Organ Size; Pregnancy; Radioimmunoassay; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

The release of brain-gut peptides during sauna bathing was studied in seven women. All women underwent a 20 min sauna bath. Their sublingual temperature rose from 36.9 +/- 0.1 degrees C to 38.6 +/- 0.2 degrees C (mean +/- SEM). A significant increase in circulating plasma vasoactive intestinal polypeptide (VIP) was observed during heat exposure, whereas plasma pancreatic polypeptide (PP), motilin and blood glucose rose and stayed significantly elevated first during the ensuing 60 min (P less than 0.05 in all cases). A similar increase in plasma insulin failed to reach statistical significance, whereas the plasma levels of somatostatin and cholecystokinin (CCK) remained unchanged. It is suggested that the plasma VIP levels are related to compensatory mechanisms during heat exposure with vasodilatation and heat loss.

Topics: Adult; Blood Glucose; Body Weight; Brain; Female; Fever; Gastrointestinal Hormones; Hemodynamics; Humans; Insulin; Middle Aged; Motilin; Pancreatic Polypeptide; Somatostatin; Steam Bath; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) levels and distribution were studied in the lung of young-adult (3-month-old) and aged (28-month-old) male Wistar rats by radioimmunoassay and immunofluorescence. VIP concentrations were reduced approximately by 60% as the animal ages. The density of VIP-immunoreactive nerve fibres was remarkably reduced within bronchial smooth muscle and bronchial glands. Moreover, the number of VIP-immunoreactive nerve cell bodies located in intraparenchymal ganglia was decreased in old rats. The density of VIP-containing perivascular plexuses was slightly reduced in senescence. The present data are indicative that VIP neuronal system is impaired in the lung of old rats. In view of the significant age-dependent loss of VIP-immunoreactive nerve fibres that supply the bronchial tree and bronchial glands it cannot be excluded that the relaxant action exerted by peptide on airway smooth muscle and the control of bronchial secretion exerted by VIP are impaired in old age.

Topics: Aging; Animals; Body Weight; Immunohistochemistry; Lung; Male; Muscle, Smooth; Organ Size; Pulmonary Artery; Pulmonary Veins; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

We have previously shown that hamster H2T pancreatic ductal cancer has a receptor for vasoactive intestinal peptide (VIP) which is not present on a cell line of human pancreatic ductal cancer (MIA). The purpose of this study was to examine the effect of chronic administration of VIP on the growth of both H2T hamster pancreatic carcinoma and MIA human pancreatic carcinoma in vivo. The growth of H2T was studied in hamsters; a control group of six hamsters received 0.1% bovine serum albumin (BSA) in saline, and two treatment groups of six hamsters each received VIP (1 and 10 nmol/kg), all administered three times a day by i.p. injection for 35 days. Both doses of VIP inhibited the growth of H2T tumor (tumor area, weight, DNA, RNA, and protein content). The growth of MIA was studied in athymic Balb/c mice, one group of 10 received 0.1% BSA and the other 10 received VIP (1 nmol/kg), both three times a day by i.p. injection for 3 months. There was no difference in tumor growth rate between the two groups. Treatment with VIP did not have any effect on body weight or size of the normal pancreas in either the hamsters or the mice. We conclude that the differential response of hamster and human pancreatic cancer to VIP treatment may be due to the presence or absence of VIP receptors.

Topics: Adenocarcinoma; Animals; Body Weight; Cricetinae; Humans; Male; Mesocricetus; Mice; Mice, Inbred BALB C; Organ Size; Pancreatic Neoplasms; Species Specificity; Vasoactive Intestinal Peptide

The eyes and urinary bladder of non-diabetic, prediabetic and diabetic Chinese hamsters were evaluated by radioimmunoassay and immunocytochemistry to determine the content and distribution of vasoactive intestinal peptide (VIP). The average concentration of VIP was increased in the eyes of all diabetic (pmol/g = 68%, pmol/organ = 50%) and prediabetic (pmol/g = 152%, pmol/organ = 115%) hamsters compared with age-matched non-diabetic animals. Immunocytochemistry showed that the elevation of VIP was primarily related to greater intensity of fluorescence of the nerve fibres in the vasculature of the choroid. The average content of VIP in the urinary bladder was greater in diabetic animals only on the basis of pmol/organ (135%) and in prediabetics on the basis of pmol/g (87%) compared with non-diabetic animals. Qualitative immunocytochemistry suggested that the elevated level of VIP was related to a larger distribution of nerve fibres in the urinary bladder of diabetic hamsters. The high level of VIP in the eyes and urinary bladder of diabetic and prediabetic hamsters is an interesting observation which should receive further study to determine whether it is an aetiological agent underlying the pathogenesis of ophthalmic complications and neurogenic bladder or the result of some pathological process which affects these organs.

Topics: 3-Hydroxybutyric Acid; Animals; Blood Glucose; Body Weight; Cricetinae; Cricetulus; Diabetes Mellitus, Experimental; Eye; Female; Hydroxybutyrates; Male; Organ Size; Prediabetic State; Urinary Bladder; Vasoactive Intestinal Peptide

Topics: Body Weight; Child, Preschool; Diarrhea; Female; Gastrointestinal Hormones; Humans; Mediastinal Neoplasms; Neurofibroma; Vasoactive Intestinal Peptide

Twenty-four male albino rats were given daily intraperitoneal injections of vasoactive intestinal polypeptide (VIP), motilin, human gastrin I (1-17) or the diluent control vehicle at a dose of 100 micrograms/kg for four consecutive days and food intake, water intake, body weight, and running wheel activity were determined every 24 hours. Animals injected with motilin or human gastrin I (1-17) exhibited decreased food intake relative to those injected with VIP or diluent, which did not differ from each other, although food intake increased reliably over days. The mean water consumption followed the same pattern as that of food intake. As expected from the above results, VIP produced weight gains as compared with rats injected with motilin or gastrin but not reliably more than after diluent. A reliable effect of trials for weight gain was the greatest on day three. Running wheel activity was not affected by injections of human gastrin I (1-17), motilin, or diluent but was reliably decreased by VIP. No significant differences existed across days. Although the results indicate that GI peptides may affect behavior when injected systemically and that like other peptides they have multiple effects, caution is urged in the interpretation of behavioral results at this time.

Topics: Animals; Behavior, Animal; Body Weight; Drinking; Eating; Gastrins; Gastrointestinal Hormones; Male; Motilin; Motor Activity; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

Cods were equipped with cannulae for drainage of the stomach and for separate perfusion of the stomach (pure sea-water) and intestine (diluted sea-water). Acidity and volume of gastric effluence were measured. Plasma immunoreactive gastrin and vasoactive intestinal polypeptide (VIP) were assayed in some experiments. The high rate of "basal" acid secretion was further elevated by i.m. administration of bombesin, but not by pentagastrin. Exogenous VIP inhibited acid secretion. Following 5 h of bombesin infusion, plasma gastrin-IR was unaffected while VIP-IR was depressed compared to saline-treated controls. The possibility that bombesin stimulates acid secretion by inhibiting VIP-release is discussed.

Topics: Animals; Body Weight; Bombesin; Female; Fishes; Gastric Juice; Gastrins; Gastrointestinal Hormones; Male; Pentagastrin; Peptides; Radioimmunoassay; Vasoactive Intestinal Peptide