Vol. 281, Issue 1, 245-252, 1997

Somatostatin Inhibition of Acid and Histamine Release by Activation of Somatostatin Receptor Subtype 2 Receptors in Rats¹

K. Aurang, J. Wang and K. C. K. Lloyd

Research and Medical Services, Department of Veterans Affairs, West Los Angeles Medical Center, and Departments of Medicine and Physiology, School of Medicine, and CURE: VA/UCLA Digestive Diseases Research Center, University of California, Los Angeles, California

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.