MODULATION BY NITRIC-OXIDE OF GASTRIC-ACID SECRETION IN TOADS

Nitric oxide (NO) is a novel chemical messenger that mediates a variet y of biological actions. This study was undertaken to investigate the effects of NO on parietal cell function. The rate of [H-3]arginine con version to [H-3]citrulline, a parameter of NO synthase activity, and N O formation (as NO2-), were inhibited by the NO synthase inhibitor,N-G -nitro-L-arginine methyl ester (L-NAME), in a concentration-dependent manner in the non-stimulated toad gastric mucosa. This range of concen trations of L-NAME provoked stimulation of H+ secretion in a similar f ashion, which was blocked by L-arginine but not by D-arginine. Pre-tre atment wi th 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 carbac hol-stimulated gastric mucosa, which was reversed by L-NAME. Carbachol and pentagastrin, but not histamine, significantly increased NO forma tion in the toad gastric mucosa. The results suggest that changes in N O synthesis in the gastric mucosa may modulate parietal cell function and that a calcium-dependent mechanism may be involved.