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 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 microg/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.
Aurang
K
K
Department of Veterans Affairs, West Los Angeles Medical Center, University of California, 90073, USA.
Wang
J
J
Lloyd
K C
KC
D000595:Amino Acid Sequence; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology*
D017481:Receptors, Somatostatin; D018723:Bethanechol; D013004:Somatostatin; D006632:Histamine; C093733:somatostatin receptor 2; D010418:Pentagastrin