Somatostatin inhibits gastrin release and acid secretion by activating sst₂ in dogs

Somatostatin is a potent inhibitor of gastrin-stimulated acid secretion by activation of somatostatin receptor type 2 (sst₂) in vivo, probably in part by blocking gastrin-stimulated histamine release from enterochromaffin- like cells expressing sst₂. We propose that activation of sst₂ may also regulate meal-stimulated acid secretion by blocking gastrin release from antral G cells. Using peptide analogs relatively selective for sst₂ (NC-8- 12), sst₃ (BIM-23058), and sst₅ (BIM-23052), we tested this hypothesis in two ways: first, in vivo by measuring plasma gastrin release during meal- stimulated acid secretion in dogs, and second, in vitro by measuring bombesin-stimulated gastrin release 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 release by 61 ± 4%, whereas the highest dose (5 nmol · kg^-1 · h^-1) inhibited gastrin release by 84 ± 3%. Only the highest doses (5 nmol · kg^-1 · h^-1) of BIM-23058 and BIM-23052 significantly inhibited gastrin release and acid secretion. In vitro, NC-8-12 (10^-9 M) reduced bombesin-stimulated gastrin release from antral G cells by 49 ± 5%, whereas BIM-23058 and BIM-23052 were at least 100-fold less effective. These results indicate that somatostatin activation of set₂, but not sst₃ or sst₅, is the major pathway for somatostatin-induced inhibition of meal-stimulated gastrin release and acid secretion.