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.
Footnotes
-
Send reprint requests to: K. C. Kent Lloyd, D.V.M., Ph.D., CURE/VAMC West LA, Building 115, Room 115, Los Angeles, CA 90073.
-
↵1 This work was supported in part by National Institutes of Health Grant DK45752 and was conducted in the Animal Models Core of National Institutes of Health Center Grant DK41301.
- Abbreviations:
- CSA
- canine serum albumin
- ECL
- enterochromaffin-like
- sstx
- somatostatin receptor subtypex
- Received August 12, 1996.
- Accepted December 23, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|