vasoactive-intestinal-peptide and Gastrointestinal-Hemorrhage

Somatostatin is a peptide synthesized in many tissues that can act as a neurotransmitter, a systemic hormone, or a local hormone, and inhibits the secretion of hormones or other cell products. A long-acting synthetic analogue of somatostatin (SMS 201-995) has been developed which when administered subcutaneously has a biologic half-life of 90 to 120 minutes and can be administered 2 or 3 times per day. SMS 201-995 can lower plasma concentrations of growth hormone and somatomedin-C in patients with pituitary acromegaly, but no controlled trials to assess symptomatic response or change in tumor size have been done. In patients with pituitary thyrotropin-producing pituitary tumors, SMS 201-995 has been remarkably effective in producing biochemical and clinical responses and is the drug of first choice in this syndrome when tumor resection is not possible. In patients with the carcinoid syndrome, SMS 201-995 effectively reduces diarrhea, is the best available drug for treatment of carcinoid flush (effective in approximately 90% of cases), and is useful in treating carcinoid crisis. Eighty-five percent of patients with pancreatic islet cell tumors that produce vasoactive intestinal peptide will respond to SMS 201-995 with a reduction in diarrhea that often has been resistant to all other therapy. SMS 201-995 may also be useful in treating the symptoms in some patients with glucagonomas, growth hormone releasing hormone-producing tumors and insulinomas. Whether SMS 201-995 has a significant effect on gut neuroendocrine tumor growth remains uncertain. Certain nonmalignant diseases of the gut respond to somatostatin, including secretory diarrhea and fistulas of unknown cause. In general, SMS 201-995 has proved safe with few significant side effects, but whether the long-term use of the drug will result in an iatrogenic form of the somatostatinoma syndrome is uncertain.

Topics: Acromegaly; Adenoma, Islet Cell; Diarrhea; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Growth Hormone; Humans; Intestinal Fistula; Malignant Carcinoid Syndrome; Octreotide; Pancreatic Neoplasms; Pancreatitis; Pituitary Neoplasms; Thyrotropin; Vasoactive Intestinal Peptide

Neurochemical and functional studies were performed to investigate and to compare the effects of resiniferatoxin and capsaicin in the rat stomach. Neonatal administration of resiniferatoxin (0.6-1.6 mumol/kg subcutaneously (s.c.)) produced a marked decrease in gastric calcitonin gene-related peptide-like immunoreactivity in both secretory and non-secretory region of the stomach. Almost complete depletion of the peptide was determined by neonatal administration of capsaicin (164 mumol/kg s.c.). Vasoactive intestinal polypeptide-like immunoreactivity was concomitantly unaffected by resiniferatoxin or capsaicin, thus showing the selectivity of action of the neurotoxins on gastric afferent fibers. Oral administration of an equimolar dose (0.3 nmol/kg) of resiniferatoxin or capsaicin together with 50% ethanol reduced at a similar extent gastric haemorrhagic lesions produced by the mucosal barrier-breaker agent. These findings provide evidence that resiniferatoxin and capsaicin may act on a common neuronal target in the rat stomach and that the acute exciting (protective) effect is of the same magnitude.

Topics: Administration, Oral; Animals; Animals, Newborn; Calcitonin Gene-Related Peptide; Capsaicin; Diterpenes; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Gastrointestinal Hemorrhage; Injections, Subcutaneous; Male; Neurons, Afferent; Neurotoxins; Rats; Stomach Ulcer; Vasoactive Intestinal Peptide

Gastric antral vascular ectasia is a recently recognized cause of chronic gastrointestinal blood loss. Immunohistochemical and electron-microscopic studies were performed on the surgically resected antrum of a patient with antral vascular ectasia. These revealed extraepithelial and intraepithelial neuroendocrine cell proliferations. Staining for a wide range of neural and endocrine markers demonstrated that these cells contain large quantities of 5-hydroxytryptamine and vasoactive intestinal polypeptide. Gastric vascular ectasia is of unknown etiology but has been associated with achlorhydria and liver cirrhosis. The findings suggest that locally released neurotransmitters may be responsible for local vasodilation and hence a propensity to bleed.

Topics: Aged; Blood Vessels; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Microscopy, Electron; Neurosecretory Systems; Pyloric Antrum; Serotonin; Telangiectasis; Vasoactive Intestinal Peptide

Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones.

Topics: Adenoma, Islet Cell; Adult; Aged; Gastrins; Gastrointestinal Hemorrhage; Glucagon; Glucagonoma; Hormones; Humans; Insulinoma; Middle Aged; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome