Inhibition by prostaglandin E2, somatostatin and secretin of histamine-sensitive adenylate cyclase in human gastric mucosa.

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(-5) mol/l), secretin (10(-9) to 10(-6) mol/l) and histamine (10(-7) to 10(-3) mol/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(-7) mol/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.