Anesthetic dependence of the inhibitory effect of neurotensin on pentagastrin-stimulated acid secretion in rats. A possible role for somatostatin.
ABSTRACT The existence of possible local mediators of the inhibitory effect of neurotensin on gastric acid secretion has not been determined. We perfused rats intragastrically with warmed saline and stimulated acid secretion with intravenous pentagastrin, 32 micrograms/kg/hr, and found that anesthesia with pentobarbital resulted in marked inhibition of acid secretion by intravenous neurotensin; however, anesthesia with urethane prevented this inhibitory effect of neurotensin from occurring. In addition, we found a significant increase in somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion in pentobarbital-anesthetized rats. Neither neurotensin nor pentagastrin infusion modified gastric luminal somatostatin-like immunoreactivity after either pentobarbital or urethane, and rats anesthetized with urethane did not show an increase of somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion. These results suggested that somatostatin-like immunoreactivity, released into the portal circulation, was necessary for exogenous neurotensin to inhibit pentagastrin-stimulated gastric acid secretion under these conditions in anesthetized rats.
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ABSTRACT: Neurotensin and somatostatin have both been shown to inhibit gastric acid secretion, but no interaction between these peptides has been demonstrated. To determine whether somatostatin might be a mediator of neurotensin's effect on pentagastrin-stimulated gastric acid secretion, we performed the following three experiments. First, we collected 0.2-ml samples of portal venous blood as frequently as every 5 min, and we confirmed a significant release of somatostatin-like immunoreactivity into portal venous blood during neurotensin-induced inhibition of acid secretion. This release of somatostatin-like immunoreactivity and inhibition of acid secretion were only seen in pentobarbital-anesthetized rats, but no sustained release of somatostatin-like immunoreactivity or inhibition of acid secretion occurred in urethane-anesthetized animals. In the second experiment, we analyzed portal plasma by high pressure liquid chromatography, and found that portal somatostatin-like immunoreactivity in blood collected during neurotensin infusion was composed of a single peak corresponding to somatostatin-14. In the third experiment, we found that infusion of antibody to somatostatin prevented neurotensin from inhibiting pentagastrin-stimulated acid secretion. Taken together, these data show that somatostatin, possibly from the stomach itself, is a necessary mediator of neurotensin's inhibitory effect in pentobarbital-anesthetized rats.Peptides 11/1992; 13(6):1175-9. DOI:10.1016/0196-9781(92)90025-X · 2.61 Impact Factor
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ABSTRACT: Cholecystokinin is a principal mediator of intestinal fat-induced inhibition of gastric acid secretion, indicating that it is an important physiological enterogastrone. Cholecystokinin has been shown to inhibit acid secretion by activation of type A CCK receptors and through a mechanism involving somatostatin. In the present study, we investigated the possibility that these two mechanisms are directly related such that activation of type A CCK receptors by CCK causes the release of somatostatin. We tested this hypothesis in vivo in a study of CCK-stimulated release of somatostatin in dogs and in vitro in a study of CCK-stimulated release of somatostatin from an enriched culture of canine fundic D cells. In dogs, IV infusion of CCK (50 pmol/kg/h, IV) significantly increased circulating somatostatin concentrations above basal. Further, systemic administration of somatostatin MAb F(ab)1 fragments of a somatostatin monoclonal antibody prevented most of CCK-induced inhibition of meal-stimulated acid secretion. In canine fundic D cells in culture, CCK-stimulated somatostatin release was blocked in a dose-dependent fashion by application of a type A CCK receptor antagonist. This study indicates that CCK activates type A CCK receptors to release somatostatin from canine fundic mucosal D cells, and accounts for somatostatin-dependent CCK-induced inhibition of acid secretion.Peptides 02/1994; 15(2):223-7. DOI:10.1016/0196-9781(94)90006-X · 2.61 Impact Factor
Article: Gut hormones in gastric function.[Show abstract] [Hide abstract]
ABSTRACT: This chapter has focused on many of the gut hormones that regulate gastric function. Gastrin remains the principal, and only, gastric hormone controlling gastric acid secretion during the cephalic, gastric and intestinal phases of secretion. Several other hormones, including cholecystokinin, peptide YY and secretin, released from intestinal endocrine cells in response to food substrates, have significant inhibitory effects on gastric acid secretion. Many of these hormones, including enteroglucagon and glucagon-like peptide, may act through paracrine release of somatostatin, which in turn acts as the final mediator of acid inhibition. In addition, several peptides contained in nerves, including gastrin releasing peptide and vasoactive intestinal peptide, have been shown to regulate gastric acid secretion and motor function. With the creation of specific monoclonal antibodies for use in in vivo immunoneutralization studies, and the development of selective chemical antagonists for use in receptor blockade experiments, the specific contributions of the different gut hormones in the regulation of gastric function, can be assessed.Baillière s Clinical Endocrinology and Metabolism 02/1994; 8(1):111-36. DOI:10.1016/S0950-351X(05)80228-9