Somatostatin inhibition of acid and histamine release by activation of somatostatin receptor subtype 2 receptors in rats

K. Aurang, J. Wang, Kevin C K Lloyd

Research output: Contribution to journalArticle

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Abstract

Peptide analogs of somatostatin with relatively selective binding affinities for specific somatostatin receptor subtypes, including SMS-201- 995 [somatostatin receptor subtype (sst)2 sst3 and sst5], NC-8-12 (sst2), BIM-23058 (sst3) and BIM-23052 (sst5), were administered i.v. to anesthetized rats to determine the somatostatin receptor subtypes involved in regulation of acid secretion stimulated by either pentagastrin (24 μg/kg/hr), bethanechol (0.2 mg/kg/hr) or histamine (5 mg/kg/hr) and in regulation of histamine release stimulated by either pentagastrin or bethanecol. Somatostatin-14 (10 nmol/kg/hr) inhibited 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 similarly to somatostatin-14, indicating that activation of sst2, sst3 and/or sst5 receptors accounts for acid inhibition induced by somatostatin. NC-8-12 dose-dependently (0.1,1, 10 and 100 nmol/kg/hr) inhibited acid secretion stimulated by pentagastrin and by bethanecol, but only the highest dose administered (100 nmol/kg/hr) blocked by half the acid response to histamine; BIM-23058 and BIM-23052 were significantly less effective. NC-8-12 (60 ± 12% of maximum) and somatostatin-14 (50 ± 14% of maximum) also blocked pentagastrin-stimulated histamine release, whereas BIM-23058 and BIM-23052 were ineffective. None of the agonists significantly reduced bethanecol-stimulated histamine release. These results indicate that somatostatin activation of sst2 receptors is the principal physiological pathway for somatostatin-induced inhibition of gastric acid secretion stimulated by either pentagastrin, bethanecol or histamine and of pentagastrin-stimulated histamine release.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume281
Issue number1
StatePublished - 1997

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ASJC Scopus subject areas

  • Pharmacology

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