Modulation by nitric oxide of gastric acid secretion in toads.

Abstract

Nitric oxide (NO) is a novel chemical messenger that mediates a variety of biological actions. This study was undertaken to investigate the effects of NO on parietal cell function. The rate of [3H]arginine conversion to [3H]citrulline, a parameter of NO synthase activity, and NO formation (as NO2-), were inhibited by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), in a concentration-dependent manner in the non-stimulated toad gastric mucosa. This range of concentrations of L-NAME provoked stimulation of H+ secretion in a similar fashion, which was blocked by L-arginine but not by D-arginine. Pre-treatment with carbachol plus ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetra-acetic acid (EGTA) prevented the effect of L-NAME on H+ secretion and drastically reduced NO synthase activity. L-arginine had an inhibitory effect on H+ secretion in non-stimulated and carbachol-stimulated gastric mucosa, which was reversed by L-NAME. Carbachol and pentagastrin, but not histamine, significantly increased NO formation in the toad gastric mucosa. The results suggest that changes in NO synthesis in the gastric mucosa may modulate parietal cell function and that a calcium-dependent mechanism may be involved.