HIGH BASAL GASTRIC-ACID SECRETION IN SOMATOSTATIN RECEPTOR SUBTYPE-2 KNOCKOUT MICE

Background & Aims: Somatostatin receptor subtype 2 (sst(2)) agonists i nhibit gastric secretion. The role of sst(2) in the regulation of acid secretion was assessed using sst(2) knockout mice and urethane to ind uce somatostatin release. Methods: Acid secretion was monitored every 10 minutes by gastric perfusion and backtitration of perfusates in fas ted, urethane-anesthetized C57/ 129 sst(2) (-/-) mice and wild-type (/+) mice. The ileal vein was cannulated for drug injection. Intragastr ic 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 the re 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 mic e. The gastrin antibody abolished the high basal acid secretion in sst (2) (-/-) mice and had no effect in wild-type mice. The somatostatin a ntibody increased basal secretion by LF-fold in wildtype and had no ef fect in knockout mice. Somatostatin 14 or the sst(2) agonist DC 32-87 inhibited pentagastrin-stimulated acid secretion in wild-type mice, bu t did not alter basal secretion in knockout mice. Conclusions: These r esults indicate that sst(2) is the main subtype whereby endogenous som atostatin suppresses gastric acid secretion through inhibition of gast rin action.