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 sst2, but not sst3 or sst5, is the major pathway for somatostatin-induced inhibition of meal-stimulated gastrin release and acid secretion.
Lloyd
K C
KC
Research Service, West Los Angeles Veterans Affairs Medical Center, California, USA.
Amirmoazzami
S
S
Friedik
F
F
Chew
P
P
Walsh
J H
JH
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D004285:Dogs; D004435:Eating; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D005755:Gastrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D011706:Pyloric Antrum; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors
D005755:Gastrins; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; D001839:Bombesin