SOMATOSTATIN INHIBITION OF ACID AND HISTAMINE-RELEASE BY ACTIVATION OF SOMATOSTATIN RECEPTOR SUBTYPE-2 RECEPTORS IN RATS

Peptide analogs of somatostatin with relatively selective binding affi nities for specific somatostatin receptor subtypes, including SMS-201- 995 [somatostatin receptor subtype (sst)(2), sst(3) and sst(5)], NC-8- 12 (sst(2)), BIM-23058 (sst(3)) and BIM-23052 (sst(5)), were administe red i.v. to anesthetized rats to determine the somatostatin receptor s ubtypes involved in regulation of acid secretion stimulated by either pentagastrin (24 mu g/kg/hr), bethanechol (0.2 mg/kg/hr) or histamine (5 mg/kg/hr) and in regulation of histamine release stimulated by eith er pentagastrin or bethanecol. Somatostatin-14 (10 nmol/kg/hr) inhibit ed pentagastrin-stimulated and bethanecol-stimulated acid secretion to basal levels but inhibited histamine-stimulated secretion to just 68% of maximum. SMS-201-995 (10 nmol/kg/hr) inhibited acid secretion simi larly to somatostatin-14, indicating that activation of sst(2), sst(3) and/or sst(5) receptors accounts for acid inhibition induced by somat ostatin. NC-8-12 dose-dependently (0.1, 1, 10 and 100 nmol/kg/hr) inhi bited acid secretion stimulated by pentagastrin and by bethanecol, but only the highest dose administered (100 nmol/kg/hr) blocked by half t he acid response to histamine; BIM-23058 and BIM-23052 were significan tly less effective. NC-8-12 (60 +/- 12% of maximum) and somatostatin-1 4 (50 +/- 14% of maximum) also blocked pentagastrin-stimulated histami ne release, whereas BIM-23058 and BIM-23052 were ineffective. None of the agonists significantly reduced bethanecol-stimulated histamine rel ease. These results indicate that somatostatin activation of sst(2) re ceptors is the principal physiological pathway for somatostatin-induce d inhibition of gastric acid secretion stimulated by either pentagastr in, bethanecol or histamine and of pentagastrin-stimulated histamine r elease.