SOMATOSTATIN INHIBITS GASTRIN-RELEASE AND ACID-SECRETION BY ACTIVATING SST(2) IN DOGS

Somatostatin is a potent inhibitor of gastrin-stimulated acid secretio n by activation of somatostatin receptor type 2 (sst(2)) in vivo, prob ably in part by blocking gastrin-stimulated histamine release from ent erochromaffin-like cells expressing sst(2). We propose that activation of sst(2) may also regulate meal-stimulated acid secretion by blockin g gastrin release from antral G cells. Using peptide analogs relativel y selective for sst(2) (NC-8-12), sst(3) (BIM-23058), and sst(5) (BIM- 23052), we tested this hypothesis in two ways: first, in vivo by measu ring plasma gastrin release during meal-stimulated acid secretion in d ogs, and second, in vitro by measuring bombesin-stimulated gastrin rel ease from an enriched culture of canine antral G cells. In vivo, a low dose (0.05 nmol.kg(-1).h(-1)) of NC-8-12 inhibited acid secretion 56 +/- 16% without blocking gastrin release. A higher dose (1 nmol.kg(-1) .h(-1)) of NC-8-12 abolished acid secretion and inhibited gastrin rele ase by 61 +/- 4%, whereas the highest dose (5 nmol.kg(-1).h(-1)) inhib ited gastrin release by 84 +/- 3%. Only the highest doses (5 nmol.kg(- 1).h(-1)) of BIM-23058 and BIM-23052 significantly inhibited gastrin r elease and acid secretion. In vitro, NC-8-12 (10(-9) M) reduced bombes in-stimulated gastrin release from antral G cells by 49 +/- 5%, wherea s BIM-23058 and BIM-23052 were at least 100-fold less effective. These results indicate that somatostatin activation of sst(2), but not sst( 3) Or sst(5), is the major pathway for somatostatin-induced inhibition of meal-stimulated gastrin release and acid secretion.