ACTIVATION OF SOMATOSTATIN RECEPTOR SUBTYPE-2 INHIBITS ACID-SECRETIONIN RATS

Somatostatin is a potent inhibitor of gastric acid secretion. Recently , at least five distinct somatostatin receptor subtypes (SSTR) have be en characterized and evaluated using relatively selective peptide anal ogues of somatostatin. We sought to determine which somatostatin recep tor subtypes are involved in peripheral regulation of gastric acid sec retion. Fasted, male Sprague-Dawley rats were anesthetized and were im planted with a double-lumen cannula in the stomach. Acid secretion was measured in gastric samples collected every 10 min by backtitration t o pH 7. After a 30-min basal period, a 2-h intravenous infusion of pen tagastrin (24 mu g.kg(-1).h(-1) iv) was started. During the second pen tagastrin hour, a l-h intravenous infusion of either vehicle (0.1% can ine serum albumin in 0.9% saline) or somatostatin receptor agonists wa s begun. The somatostatin receptor agonists included peptides with rel ative 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, fro m 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% o f 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 ac id secretion by activation of SSTR(2) receptors.