Inhibition by Prostaglandin E2, Somatostatin and Secretin of Histamine-Sensitive Adenylate Cyclase in Human Gastric Mucosa

Abstract

The effects of prostaglandin E₂ (PGE₂), somatostatin and secretin on gastric mucosal adenylate cyclase (AC) and their interactions with the histamine-sensitive AC were studied using biopsy specimens of normal human gastric mucosa. PGE₂ (10^-7 to 10^-3 mol/l), somatostatin (10^-9 to 10^-5mol/l), secretin (10^-9 to 10^-6mol/l) and histamine (10^-7 to 10^-3mol/l), all stimulated mucosal AC in a concentration-dependent manner. Besides this effect, PGE₂, somatostatin and secretin significantly inhibited the histamine-activated enzyme at concentrations as low as 10^-10 to 10^-7 (PGE₂), 10^-9 to 10^-6 (somatostatin) and 10^-9 to 10^-5 mol/l (secretin). They were more potent than cimetidine which initiated inhibition at concentrations exceeding 10^-7mol/l. The data show that PGE₂, somatostatin and secretin have a dual action on AC: (1) they all activate human gastric AC on their own, and (2) they all inhibit the histamine-sensitive enzyme at the parietal cell level at nanomolar concentrations, thus underlining the concept that hormonal control is essential in the regulation of gastric acid secretion.