High basal gastric acid secretion in somatostatin receptor subtype 2 knockout mice

Background & Aims: Somatostatin receptor subtype 2 (sst(2)) agonists inhibit gastric secretion. The role of sst(2) in the regulation of acid secretion was assessed using sst(2) knockout mice and urethane to induce somatostatin release. Methods: Acid secretion was monitored every 10 minutes by gastric perfusion and backtitration of perfusates in fasted, urethane-anesthetized C57/ 129 sst(2) (-/-) mice and wild-type (+/+) mice. The ileal vein was cannulated for drug injection. Intragastric pH and serum gastrin were monitored 1 hour after anesthesia without perfusion. Results: Gastric pH values were lower in sst(2) (-/-) mice (3.8 +/- 0.3) than in wild-type mice (7.1 +/- 0.1, P < 0.05), and there was no difference in gastrin levels. Basal acid output per 2 hours was 10-fold higher in sst(2) knockout mice compared with wild-type mice. The gastrin antibody abolished the high basal acid secretion in sst(2) (-/-) mice and had no effect in wild-type mice. The somatostatin antibody increased basal secretion by LF-fold in wildtype and had no effect in knockout mice. Somatostatin 14 or the sst(2) agonist DC 32-87 inhibited pentagastrin-stimulated acid secretion in wild-type mice, but did not alter basal secretion in knockout mice. Conclusions: These results indicate that sst(2) is the main subtype whereby endogenous somatostatin suppresses gastric acid secretion through inhibition of gastrin action.