vasoactive-intestinal-peptide and Duodenal-Ulcer

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Cimetidine; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Glycoproteins; Humans; Intestinal Mucosa; Peptic Ulcer; Receptors, Histamine; Secretin; Secretory Rate; Somatostatin; Stomach Ulcer; Vasoactive Intestinal Peptide

The protective effect of capsaicin-sensitive sensory nerve (CSSN) activation was recently demonstrated in human gastric mucosa. We here examined changes in neuropeptides, specifically Substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) in patients with chronic gastritis or ulcer. Furthermore changes in neprilysin levels, which hydrolyse these neuropeptides, were determined. Gastric biopsies were obtained from both lesion- and normal-appearing mucosa of 57 patients. The presence of H. pylori infection was verified with rapid urease assay. Neuronal and non-neuronal levels of SP, VIP, CGRP and neprilysin activity were determined in freshly frozen biopsies. Immunohistochemical localization of neprilysin was performed in 30 paraffin embedded specimens. We here found that neuronal SP levels decreased significantly in normally appearing mucosa of patients with gastritis while levels of non-neuronal SP increased in diseased areas of gastritis and ulcer. The presence of H. pylori led to further decreases of SP levels. The content of VIP in both disease-involved and uninvolved mucosa, and expression of neprilysin, markedly decreased in patients with gastritis or ulcer. Since VIP, as well as SP fragments, formed following hydrolysis with neprilysin is recognized to have gastroprotective effects, decreased levels of VIP, SP and neprilysin may predispose to cellular damage.

Topics: Adult; Calcitonin Gene-Related Peptide; Duodenal Ulcer; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neprilysin; Neurons; Peptic Ulcer; Substance P; Ulcer; Vasoactive Intestinal Peptide; Young Adult

Stomach and small bowel both influence gastrointestinal motility. We studied which portion of the stomach was essential for the regulation of gastrointestinal movement and determined the role of vasoactive intestinal polypeptide in this regulation. The study subjects consisted of 45 controls, 46 patients after subtotal gastrectomy, and 13 patients after total gastrectomy for stomach cancer. Orocecal transit time was measured, using the hydrogen breath test, to represent gastrointestinal movement, while plasma vasoactive intestinal polypeptide level was simultaneously assessed. The orocecal transit times in the study groups were (means +/- SD) 91.1 +/- 45.0, 57.1 +/- 34.3, and 60.8 +/- 34.8 min, respectively (P < 0.01). In the subtotal gastrectomy patients, age showed a negative correlation with orocecal transit time (r = -0.388; P < 0.01). In the total gastrectomy patients, no particular demographic factor influenced orocecal transit. Plasma vasoactive intestinal polypeptide levels in the three groups were 20.7 +/- 10.8, 22.7 +/- 10.9, and 20.6 +/- 9.1 pg/ml, respectively (NS). We conclude that both types of gastrectomies enhanced gastrointestinal movement, showing a similar effect, and that the distal stomach plus pylorus are most likely to exert an important inhibitory mechanism in the regulation of this movement. Vasoactive intestinal polypeptide is not a major peptide mediating this regulation.

Topics: Aged; Breath Tests; Case-Control Studies; Duodenal Ulcer; Female; Gastrectomy; Gastrointestinal Transit; Humans; Hydrogen; Male; Pylorus; Stomach; Stomach Neoplasms; Vasoactive Intestinal Peptide

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on duodenal mucosal HCO3- secretion and ulcerogenic responses induced by mepirizole in anesthetized rats were examined and compared with those of vasoactive intestinal polypeptide (VIP). Animals were given mepirizole (200 mg/kg, s.c.) for induction of duodenal ulcers, and gastric acid and duodenal HCO3- secretions were measured with or without pretreatment of PACAP-27 or VIP. Mepirizole increased acid secretion and induced hemorrhagic lesions in the proximal duodenum within 6 h. Intravenous bolus injection or infusion of PACAP-27 (4 and 8 nmol/kg or 8 nmol/kg/h) increased duodenal HCO3- secretion even in the presence of mepirizole, without effect on acid secretion, and significantly reduced the severity of duodenal lesions caused by mepirizole. In contrast, VIP (8 nmol/kg, i.v.) given by bolus injection significantly decreased acid secretion induced by mepirizole, in addition to stimulation of HCO3- secretion, and prevented duodenal lesions in response to mepirizole. These results suggest that PACAP-27 increases duodenal HCO3- secretion and this action may be important in maintaining the duodenal mucosal integrity against acid, and VIP affords duodenal protection by both increasing duodenal HCO3- secretion and decreasing acid secretion. The reason for the different effects of PACAP and VIP on acid secretion is unknown.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bicarbonates; Duodenal Ulcer; Duodenum; Epirizole; Gastric Acid; Intestinal Mucosa; Male; Neuropeptides; Neurotransmitter Agents; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; Vasoactive Intestinal Peptide

The effect of cigarette smoke and nicotine on duodenal mucosal bicarbonate secretion (DMBS) was studied in rats. Cigarette smoke but not intravenous nicotine administered acutely to anesthetized rats via a tracheostomy tube stimulated DMBS by 47 +/- 6%. The increase was neurally mediated via atropine-sensitive postganglionic cholinergic neurons. Introduction of cigarette smoke after the infusion of vasoactive intestinal peptide and porcine histidine isoleucine (PHI) also caused a delayed increase in DMBS. However, the magnitude of this increase was similar to that seen in control non-peptide-infused rats. The increase in bicarbonate secretion predominantly involved Brunner's glands. Rats exposed to cigarette smoke for 4 and 8 days before direct instillation of smoke via tracheostomy tube did not show any increase in their DMBS. These studies indicate that in the rat, cigarette smoke increases DMBS, most likely secreted by the Brunner's glands. The increase is neurally mediated via atropine-sensitive postganglionic cholinergic neurons. Gastroenteric neuropeptides do not exert any influence on cigarette smoke-mediated DMBS secretion in the rat. Unlike acute exposure to cigarette smoke, chronic exposure (4 and 8 days) of rats to cigarette smoke abolishes increase in DMBS induced by subsequent exposure to cigarette smoke. This last observation may, in part, may explain the tendency of chronic smokers who have duodenal bulb ulcers to show greater propensity to higher rate of recurrence and protracted healing.

Topics: Animals; Atropine; Bicarbonates; Brunner Glands; Duodenal Ulcer; Duodenum; Gastrointestinal Hormones; Hexamethonium; Intercellular Signaling Peptides and Proteins; Intestinal Mucosa; Male; Neurotransmitter Agents; Peptides; Rats; Rats, Sprague-Dawley; Recurrence; Reserpine; Smoking; Tetrodotoxin; Vagotomy; Vagus Nerve; Vasoactive Intestinal Peptide; Wound Healing

The synthetic peptides AC-Glu-Phe-Phe (NO2)-Arg-amide (peptide VP) and AC-Ile-Glu-Phe-Phe (NO2)-Arg-amide (peptide VIP) are more readily hydrolyzed by human pepsin in gastric juice of patients of gastritis than those of duodenal ulcer and normal subjects. The kinetic parameters suggest that S3 subsite of the enzyme plays a role in the elevation of enzyme activity in gastric disease.

Topics: Amino Acid Sequence; Binding Sites; Duodenal Ulcer; Gastric Juice; Gastritis; Humans; Kinetics; Molecular Sequence Data; Oligopeptides; Pepsin A; Reference Values; Substrate Specificity; Vasoactive Intestinal Peptide

Topics: Adult; Aged; Aging; Animals; Bicarbonates; Dinoprostone; Duodenal Ulcer; Duodenum; Female; Humans; Hydrochloric Acid; Male; Middle Aged; Rats; Vasoactive Intestinal Peptide

A primary duodenal small-cell neuroendocrine carcinoma was found in an elderly man who presented with upper abdominal pain. Although metastatic small-cell carcinoma was documented by liver biopsy, the primary lesion was not identified until postmortem examination. The latter tumor, which ulcerated the duodenal mucosa, was composed of small ovoid cells with sparse cytoplasm and granular chromatin. Electron microscopy revealed cytoplasmic dense-core granules. Immunocytochemical study demonstrated the presence of neuron-specific enolase, Leu 7 antigen, chromogranin, epithelial membrane antigen, and vasoactive intestinal polypeptide within tumor cells. However, there was no evidence of a clinical endocrinopathy. This case emphasizes the need to include the duodenum as a possible primary site when metastatic small-cell neuroendocrine carcinoma is seen in the absence of apparent pulmonary disease.

Topics: Aged; Carcinoma, Small Cell; Duodenal Neoplasms; Duodenal Ulcer; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Neoplasm Metastasis; Vasoactive Intestinal Peptide

Topics: Animals; Brunner Glands; Cysteamine; Duodenal Ulcer; Intestinal Mucosa; Male; Rats; Rats, Inbred Strains; Regional Blood Flow; Secretin; Vasoactive Intestinal Peptide

To further elucidate the pathophysiological role of peptide hormones in duodenal ulcer (DU) disease, several endocrine, paracrine and neurocrine peptides were determined radioimmunologically in biopsies of gastroduodenal mucosa obtained endoscopically in 8 subjects without upper gastrointestinal disease, and in 8 duodenal ulcer patients. The DU patients had a BAO of 6.6 +/- 1.9 and a PAO of 41.8 +/- 6.1 mEq/h. In DU patients, a lack of the acid and gastrin-release inhibiting agent somatostatin was found neither in antral nor in fundic mucosa (185 +/- 60 vs 83 +/- 19 pmol/g tissue wet weight in controls). Basal and peak acid outputs of DU patients were positively correlated with fundic somatostatin concentrations (p less than 0.01). While gastrin levels were not significantly elevated in the antrum of DU patients, the mucosal content of potentially releasable gastrin of the duodenal bulb and the descending duodenum was higher than in controls (p less than 0.01). In the whole duodenum, CCK-like immunoreactivity was also more abundant in DU patients than in controls, whereas GIP and motilin did not exhibit characteristic profiles. Presumably as a reactive phenomenon, the mucosal levels of the peptidergic neurotransmitters VIP and substance P were markedly increased in the proximal duodenum of DU patients.

Topics: Adult; Cholecystokinin; Duodenal Ulcer; Duodenum; Female; Gastric Inhibitory Polypeptide; Gastrins; Hormones; Humans; Intestinal Mucosa; Male; Middle Aged; Motilin; Somatostatin; Stomach; Substance P; Tissue Distribution; Vasoactive Intestinal Peptide

The mechanisms by which the potent antiinflammatory agent, mepirizole, causes duodenal ulceration were investigated in the rat. After subcutaneous administration of 200 mg/kg of mepirizole, basal gastric acid secretion remained unchanged for 5 h but duodenal alkaline output, reliably measured, decreased significantly (p less than 0.05) within 2 h. The decrease was maximal (-45%) at 3 h and persisted for a total of 6 h. The duodenal alkaline secretion returned to near normal by 24 h. A dose-response study showed that the threshold ulcerogenic dose of mepirizole (30 mg/kg) did not significantly reduce alkaline secretion, whereas higher doses did. Plasma levels of immunoreactivity of gastrin, pancreatic polypeptide, vasoactive intestinal polypeptide, and secretin were not changed at either 6 or 24 h after oral mepirizole. Vasoactive intestinal peptide levels in the duodenal mucosa were increased by 158% at 24 h after administration. Secretin levels in the duodenal mucosa were decreased by greater than 60% at both 6 and 24 h after drug treatment. Intravenous secretin (1 CU/kg X h) had no effect on duodenal alkaline secretion in either saline- (154 mM NaCl) or mepirizole-treated animals. Exogenous 16,16-dimethyl prostaglandin E2 (10 micrograms/kg X h, i.v.) reversed the action of mepirizole on duodenal alkaline secretion. These findings suggest that mepirizole causes a reduction in duodenal alkaline secretion that can be reversed by administration of an exogenous prostaglandin.

Topics: 16,16-Dimethylprostaglandin E2; Alkalies; Animals; Dose-Response Relationship, Drug; Duodenal Ulcer; Duodenum; Epirizole; Gastric Acid; Gastrins; Injections, Subcutaneous; Male; Pyrazoles; Radioimmunoassay; Rats; Rats, Inbred Strains; Secretin; Time Factors; Vasoactive Intestinal Peptide

Topics: Adult; Duodenal Ulcer; Female; Gastrointestinal Hormones; Humans; Male; Middle Aged; Peptic Ulcer; Vasoactive Intestinal Peptide

Topics: Betazole; Blood Glucose; Duodenal Ulcer; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Metoclopramide; Neurotensin; Pentagastrin; Peptides; Pyloric Antrum; Secretory Rate; Somatostatin; Vasoactive Intestinal Peptide

Topics: Acute Disease; Adolescent; Adult; Duodenal Ulcer; Female; Gastrointestinal Hormones; Hepatitis; Humans; Liver Cirrhosis, Alcoholic; Male; Pancreatitis; Stomach Neoplasms; Vasoactive Intestinal Peptide

Relationships between hormonal secretions from the GI tract and gastric functional and/or pathological abnormalities could be studied according to 2 main lines : 1) gastric secretory changes could be the main symptom of hormonal secretory tumors, i.e. acid hypersecretion in the Zollinger Ellison syndrome, acid hyposecretion in pancreatic cholera and in somatostatinoma. In these cases, hormonal hypersecretion is directly responsible for the functional disturbances and the related symptoms; 2) gastric pathological conditions are sometimes accompanied by changes in hormonal secretion, but the level of interdependence is variable : high blood gastrin is directly depending upon the atrophic gastritis in pernicious anemia; this mechanism was also suggested in case of gastric carcinoma. Concerning ulcer disease, numerous problems are unsolved in respect to blood gastrin (basal and stimulated) abnormalities, as well as somatostatin and GIP secretions.

Topics: Aged; Anemia, Pernicious; Cholera; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Humans; Pancreatic Diseases; Pancreatic Neoplasms; Somatostatin; Stomach Diseases; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

In medical practice, diagnostic and therapeutic aspects of gastrointestinal hormones attract interest. Gastrin--in the form of pentagastrin--can be used for gastric secretory analysis and, in the analysis of exocrine pancreatic function, secretin and cholecystokinin-pancreozymin can be employed as stimulants. Diagnosis of hormone-producing tumors is possible by radioimmunological determination of serum levels of the hormone in question: so, dramatically high gastrin levels can be found in the Zollinger-Ellison syndrome while in the Verner-Morrison syndrome, VIP (vasoactive intestinal peptide) values are significantly elevated.--The therapeutic use of gastrointestinal hormones (gastrin, secretin) is waiting in the wings.

Topics: Cholecystokinin; Duodenal Ulcer; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Pancreatic Diseases; Pancreatic Neoplasms; Pentagastrin; Secretin; Vasoactive Intestinal Peptide