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PubMed1989

Synthesis and secretion of vasoactive intestinal peptide by rat fetal cerebral cortical and hypothalamic cells in culture.

To establish the neurosecretory activity of brain vasoactive intestinal peptide (VIP)ergic neurons and to characterize the molecular forms of secretion of these cells, fetal cerebrocortical and hypothalamic cells were grown in primary cultures for periods up to 4 weeks, their regulation by depolarization and calcium and sodium channel active agents was studied, and the chromatographic patterns of cell and medium VIP were determined. Mechanically dispersed cultured fetal telencephalic and diencephalic cells showed a progressive increase in immunoreactive VIP in both cells and media, reaching maximum values between 110-290 pg/mg protein.culture plate on days 15-20. Immunoreactive VIP in both cells and media corresponded almost exclusively to VIP-28 on exclusion chromatography and HPLC, and was identical to the form extracted from whole fetal brain. This indicates that both the stored and secreted forms of VIP are the mature 28-amino acid-containing peptide. To determine the influence of membrane depolarization on VIP release, the potassium concentration in the medium was increased to 30 and 56 mM, inducing a marked increase in medium VIP concentrations. The effects of K+ were dependent on Ca2+ transport, since release was blocked by the addition of verapamil, a Ca2+ channel blocker (20 microM). VIP release was stimulated by Na+ channel activation using the drug veratridine (100 microM); this effect was blocked by tetrodoxin. The influence of GH-releasing factor (GRF) on VIP release was studied by adding GRF (10(-9)-10(-7) M), alone or in the presence of anti-rGRF immunoglobulins (antirat GRF immunoglobulin G) to the incubation medium. Rat GRF stimulated VIP release and the simultaneous addition of antirat GRF immunoglobulin G blocked this effect. These findings confirm that VIP regulation by brain cells corresponds to the well defined patterns of membrane activation observed in other neuronal systems. They, furthermore, demonstrate that VIP release is under GRF influence.

Animals↗
PubMed1976

[Participation of the stomach and small intestine in the mechanism of insulin secretion following oral glucose administration].

In chronic experiments on 22 dogs, four of them having fistulas of oesophagus, stomach, and duodenum combined with artificial dissociation of stomach from duodenum, the per os and intraduodenal administration of glucose increased concentration of glucose and immunoreactive insulin in the peripheral blood, while intrastomach administration of glucose increased the immunoreactive insulin concentration alone. The data obtained suggest three phases of insulin mobilization: the first is due to neural mechanisms and occurs at the moment of contact between glucose and mucosa of the mouth, stomach, and duodenum; the second phase seems to be due to enterohormones and is activated by the contact between glucose and mucosa of the mouth, stomach, and duodenum; the third phase is associated with resorptive hyperglycemia which directly activates the B-cells.

Animals↗
PubMed1988

A comparison of the effects of vasoactive intestinal polypeptide on secretion from the submaxillary gland of the sheep and pig.

The effects, on secretion of fluid and protein from the submaxillary gland of intracarotid injections of acetylcholine or vasoactive intestinal polypeptide (VIP), and intracarotid infusions of VIP during a background of muscarinic stimulation, were examined in sheep and pigs. Intracarotid injections of VIP produced secretion of saliva from the ovine gland which continued after administration of atropine, phentolamine and propranolol. The protein concentration of this saliva was over 5-fold greater than that secreted in response to acetylcholine. Intracarotid injection of VIP did not evoke secretion from the porcine submaxillary gland but increased 3-fold the protein concentration in saliva evoked by subsequent intracarotid injection of acetylcholine. Intracarotid infusions of VIP in sheep produced dose-related increases in both flow (up to 1.9-fold) and protein concentration (up to 42-fold) of submaxillary saliva secreted in response to a background infusion of bethanechol. In pigs, intracarotid infusions of VIP at 0.015, 0.15 and 1.5 nmol/min produced increases in both flow and protein concentration of bethanechol-evoked saliva. The increases in protein concentration (up to 2.8-fold) were dose-related, but the increases in flow were not, being ca. 25% with each dose of VIP. The experiments provide evidence that VIP may effect mobilization of protein into saliva even in a species (pig) in which VIP does not evoke secretion of fluid.

Acetylcholine↗
PubMed1997

Comparison of effects of uroguanylin, guanylin, and Escherichia coli heat-stable enterotoxin STa in mouse intestine and kidney: evidence that uroguanylin is an intestinal natriuretic hormone.

BACKGROUND: Uroguanylin and guanylin are intestinal peptides that activate a receptor-guanylate cyclase, which is also a receptor for Escherichia coli heat-stable enterotoxin (STa). These peptides may have a role in the body's regulation of fluid and electrolytes. METHODS: STa, bioactive guanylin, and bioactive uroguanylin were evaluated for effects in: 1) the suckling mouse intestinal fluid secretion assay; 2) an in vitro suckling mouse intestinal loop assay; 3) an intestinal receptor autoradiography assay; 4) a control or agonist-stimulated assay for cGMP response in T84 cells; and 5) an in vivo renal function assay in mice. RESULTS: In vivo, orally administered uroguanylin and STa but not guanylin, stimulated intestinal fluid secretion. All three peptides activated intestinal guanylate cyclase and had common intestinal receptors. In vitro, after pretreatment with chymotrypsin, only uroguanylin and STa retained agoinst activity. Chymostatin preserved guanylin activity. STa and uroguanylin induced diuresis, natriuresis, and kaliuresis. Guanylin was less potent than uroguanylin and STa. CONCLUSIONS: The results suggest that the endogenous intestinal peptides, uroguanylin and guanylin, regulate water and electrolyte homeostasis both through local effects on intestinal epithelia and endocrine effects on the kidney.

Animals↗
PubMed1981

Antibody response to the lipopolysaccharide and protein antigens of Salmonella typhi during typhoid infection. II. Measurement of intestinal antibodies by radioimmunoassay.

Antibodies to the lipopolysaccharide (LPS) and protein antigens of S. typhi in secretions of small intestine obtained from 12 typhoid patients, four typhoid carriers and 16 non-typhoid control subjects were measured by a solid-phase radioimmunoassay technique. Intestinal secretions obtained from typhoid patients as a group had significantly higher anti-LPS and anti-protein antibodies than those from the control group. These antibodies were both IgM and IgA classes. There was no correlation between the IgM or IgA antibody levels in serum and those in the intestinal secretions. In the intestinal secretions obtained from typhoid carriers, on the other hand, only IgA-class antibodies to the LPS and protein antigens of S. typhi were present at high levels.

Adolescent↗
PubMed1994

Vasoactive intestinal polypeptide (VIP) secretion and refractory diarrhea in patients with AIDS or AIDS-related complex (ARC).

Elevated plasma levels of vasoactive intestinal polypeptide (VIP) (as assessed by a radio-immunoassay), were found in 7/11 patients with AIDS or AIDS-related Complex (ARC), evaluated because of prolonged intractable diarrhea with either an infectious (6 cases) or a non-infectious (5 cases) etiology. Six subjects have been treated with the somatostatin analogue octreotide, which gave both a favourable clinical response and a significant reduction in plasma VIP concentrations. Evaluation of plasma VIP levels may provide a pathophysiological basis for explaining the efficacy of octreotide therapy in HIV-infected patients suffering from both infectious and non-infectious refractory diarrhea.

AIDS-Related Complex↗
PubMed1978

Studies on translocation of immunoglobulins across intestinal epithelium. III. Failure of cholera enterotoxin to stimulate secretion of IgA by rabbit intestine.

We tested the hypothesis that the secretion of IgA into intestinal fluids is modulated by increases in epithelial cell cyclic AMP. Cholera enterotoxin instilled into intestinal loops of rabbits did not induce IgA secretion, even though an appropriate fluid response was obtained. The findings, therefore, do not support the hypothesis.

Animals↗
PubMed1988

Preoperative localization of a vasoactive intestinal peptide-secreting tumor by transhepatic portal venous sampling.

A 35-yr-old woman presented with episodic secretory diarrhea. Plasma vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP) venous levels were elevated. An abdominal computerized tomographic scan showed an enlarged head of the pancreas but no discrete mass. Superselective abdominal arteriography also failed to localize the tumor. Transhepatic portal vein sampling for VIP and PP showed a large increase in VIP and PP in the veins draining the head of the pancreas, with the highest levels being found at the union of the posterior superior pancreaticoduodenal vein with the portal vein. Surgical exploration confirmed this tumor location and a 2 x 3 cm encapsulated benign tumor was enucleated from the posterior surface of the head of the pancreas. Postoperatively, VIP and PP levels decreased to normal and the diarrheal episodes ceased. This case report demonstrates the usefulness of transhepatic portal vein sampling in localization of VIPomas if other radiological modalities are not helpful.

Adenoma, Islet Cell↗
PubMed1996

Salt and water homeostasis: uroguanylin is a circulating peptide hormone with natriuretic activity.

Guanylin and uroguanylin are small, heat-stable peptides that were initially isolated from rat jejunum and opossum urine, respectively. Both peptides bind to and activate a common set of apical membrane receptors that contain a guanylate cyclase catalytic domain within the receptor molecule. The guanylin/uroguanylin receptors are found on the luminal surface of epithelial cells lining the intestinal tract and renal proximal tubules as well as in other organs. Activation of receptor-guanylate cyclase signaling molecules by uroguanylin or guanylin elicits large increases in guanosine cyclic 3'-5' monophosphate (cGMP) production. Intracellular accumulation of this second messenger in target cells leads to the stimulation of intestinal chloride secretion, culminating in the enhancement of salt and water secretion into the intestinal lumen as well as increases in urinary sodium, potassium, and water excretion by actions of cGMP in the renal tubules. Uroguanylin and guanylin are produced throughout the intestinal mucosa and, surprisingly, uroguanylin messenger RNA (mRNA) is also expressed in both atria and ventricles of the heart. Both proguanylin and prouroguanylin are inactive polypeptides, and activation is accomplished by cleavage and release of the COOH-terminal peptides, guanylin and uroguanylin. Uroguanylin is postulated to function as an intestinal natriuretic hormone because: (1) prouroguanylin and uroguanylin both circulate in the plasma of normal animals; (2) uroguanylin is the predominant peptide agonist appearing in the filtrate and, thus, in urine; (3) the receptors for uroguanylin are localized to the apical membranes of renal tubular cells; (4) uroguanylin is substantially more potent than guanylin in eliciting a natriuresis; and (5) uroguanylin is expressed in the duodenum and myocardium, which are appropriate sites in the body for the production and release of a hormone that acts as a natriuretic agonist in vivo. The hypothesis that uroguanylin links the intestine with the kidney in an endocrine axis also predicts that the secretion of uroguanylin from the intestinal mucosa will be influenced by dietary levels of salt. Accordingly, plasma levels of uroguanylin or prouroguanylin should be influenced by oral salt loads. Future investigations will focus on the basic endocrinology of uroguanylin to provide answers to this intriguing question. In conclusion, uroguanylin is a candidate for a physiological role as an intestinal natriuretic hormone. Key features of the biology of uroguanylin provide a putative explanation for the substantial natriuresis that occurs in human subjects and experimental animals after an oral salt load. Moreover, uroguanylin and guanylin participate cooperatively in an intrinsic pathway for regulation of intestinal salt and water transport, thus providing another means of influencing salt and water homeostasis in addition to the renal actions of uroguanylin.

Animals↗
PubMed1977

[Secretion of small intestinal enzymes after section of the pancreatic duct].

In chronic experiments on dogs, soon after ligation of the pancreatic duct, amylase increases in the peripheral blood as well as the total amylase and lipase release in liquid and solid portions of the secret from isolated parts of the small intestine. The alpha--amylase release was shown to depend on the level of the blood amylolytic activity and on secretory activity of small intestine. The alpha--amylase and lipase release is more increased at mechanical rather than at chemical stimulation of the small intestine. After the secretory function of the pancreas is excluded, two stages of compensatory--adaptive changes occur in the secretory activity of small intestine: first the compensation is due to less energy--consuming processes (recretion of the blood enzymes), and further the compensatory mechanisms of the small intestine become involved.

Amylases↗