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

Kevin C K Lloyd, S. Amirmoazzami, F. Friedik, P. Chew, J. H. Walsh

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume272
Issue number6 35-6
StatePublished - Jun 1997

Keywords

  • G cells
  • Somatostatin receptors
  • Stomach

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

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