Examination of somatostatin involvement in the inhibitory action of GIP, GLP-1, amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue

Br J Pharmacol. 1998 Nov;125(5):1081-7. doi: 10.1038/sj.bjp.0702160.

Abstract

1. The effect of a new type 2 selective somatostatin (SRIF) receptor antagonist (DC-41-33) on somatostatin-induced inhibition of pentagastrin-stimulated gastric acid secretion in conscious, chronic gastric fistula equipped rats was studied. 2. Infused intravenously, DC-41-33 dose-dependently inhibits SRIF-induced inhibition of pentagastrin-stimulated gastric acid secretion with an IC50 of 31.6+/-1.2 nmol kg(-1) versus 10 nmol kg(-1) SRIF and blocks the inhibitory effects of SRIF when simultaneously co-infused. Its effectiveness provides additional evidence that SRIF-inhibition of gastric acid release is a SRIF type 2 receptor-mediated process. 3. DC-41-33 is able to completely reverse the inhibitory effect of glucose-dependent insulinotropic polypeptides, GIP and GIP-(1-30)NH2, and glucagon-like polypeptide, GLP-1(7-36)NH2, on pentagastrin-stimulated gastric acid secretion thus confirming that they exert these effects through stimulation of endogenous SRIF release. 4. DC-41-33 only partially blocks potent amylin and adrenomedullin-induced inhibition of gastric acid secretion, therefore suggesting that somatostatin may not function as a primary mediator in the action of these peptides. 5. Our results indicate that DC-41-33, is a potent in vivo inhibitor of exogenous and endogenous SRIF in rats. It represents a new class of SRIF analogues which should eventually provide excellent tools for further evaluating the many physiological roles of SRIF and its five receptor subtypes.

MeSH terms

  • Adrenomedullin
  • Amyloid / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Gastric Acid / metabolism*
  • Gastric Inhibitory Polypeptide / pharmacology
  • Gastrointestinal Hormones / pharmacology
  • Glucagon / pharmacology
  • Glucagon-Like Peptide 1
  • Islet Amyloid Polypeptide
  • Male
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology
  • Protein Precursors / pharmacology
  • Rats
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Receptors, Somatostatin / metabolism
  • Somatostatin / metabolism*

Substances

  • Amyloid
  • Gastrointestinal Hormones
  • Islet Amyloid Polypeptide
  • Peptide Fragments
  • Peptides
  • Protein Precursors
  • Receptors, Somatostatin
  • Adrenomedullin
  • Somatostatin
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • somatostatin receptor 2