Stimulatory effects of nitric oxide donors on histamine release in isolated rat gastric mucosal cells

We previously reported stimulatory effects of endogenous and exogenous nitric oxide (NO) on gastric acid secretion. In the present study, we investigated effects of NO donors on release of histamine, which is related to acid secretion, in isolated rat gastric mucosal cells. NO donors such as (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexanamide (NOR 1) and sodium nitroprusside significantly augmented the histamine release. It was inhibited by 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-amide(carboxy-PTIO), a NO scavenger, and 6-(phenylamino)-5,8-quinolinedione (LY83583), a soluble guanylate cyclase inhibitor. Dibutyryl cyclic GMP also stimulated histamine release. These results suggest that NO donors act on cyclic GMP pathway in isolated gastric mucosal cells, resulting in facilitation of histamine release. NO may stimulate gastric acid secretion through histamine release from the histamine-containing cells, possibly enterochromaffin-like cells.