ACTIVATION OF SOMATOSTATIN RECEPTOR SUBTYPE-2 INHIBITS ACID-SECRETION IN RATS

Somatostatin is a potent inhibitor of gastric acid secretion. Recently, at least five distinct somatostatin receptor subtypes (SSTR) have been characterized and evaluated using relatively selective peptide analogues of somatostatin. We sought to determine which somatostatin receptor subtypes are involved in peripheral regulation of gastric acid secretion. Fasted, male Sprague-Dawley rats were anesthetized and were implanted with a double-lumen cannula in the stomach. Acid secretion was measured in gastric samples collected every 10 min by backtitration to pH 7. After a 30-min basal period, a 2-h intravenous infusion of pentagastrin (24 mu g.kg(-1).h(-1) iv) was started. During the second pentagastrin hour, a l-h intravenous infusion of either vehicle (0.1% canine serum albumin in 0.9% saline) or somatostatin receptor agonists was begun. The somatostatin receptor agonists included peptides with relative specificity for SSTR(1-5) (somatostatin-14; 10 nmol.kg(-1).h(-1)); SSTR(2), SSTR(3), and SSTR(5) [SMS-(201--995); 10 nmol kg(-1).h(-1)]; SSTR(2) (1-1,000 nmol kg(-1).h(-1)); SSTR(3) (10-1,000 nmol.kg(-1).h(-1)); and SSTR(5) (10-1,000 nmol.kg(-1).h(-1)). The SSTR(2) agonist decreased pentagastrin-stimulated acid secretion dose dependently, from 82 +/- 7% of maximum acid output at 1 nmol.kg(-1).h(-1) to 4 +/- 7% of maximum at 100 nmol.kg(-1).h(-1). At 10 nmol.kg(-1).h(-1), the SSTR(2) agonist inhibited acid secretion (40 +/- 7% of maximum) similarly to somatostatin (37 +/- 4% of maximum) and SMS-(201--995) (31 +/- 4% of maximum). The SSTR(2) agonist inhibited acid secretion approximately 10- to 100-fold more potently than either the SSTR(3) or the SSTR(5) agonist. These results indicate that somatostatin regulates gastric acid secretion by activation of SSTR(2) receptors.