INHIBITORY EFFECTS OF NITRIC-OXIDE DONORS ON NITRIC-OXIDE SYNTHESIS IN RAT GASTRIC MYENTERIC PLEXUS

We investigated whether nitric oxide (NO) exerts an inhibition on its own synthesis in the gastric myenteric plexus in rats. Nonadrenergic, noncholinergic relaxations in response to transmural electrical stimul ation (TS) were markedly antagonized by NG-nitro-L-arginine methyl est er, (10(-4) M) and abolished by tetrodotoxin (10(-6) M). Pretreatment with various NO donors {3-morpholino-sydnonymide [SIN-1 (3 x 10(-7) to 3 x 10-6 M)], S-nitroso-N-acetylpenicillamine (10(-6) to 10(-5) M), s odium nitroprusside (10(-8) to 3 x 10(-8) M) and 8-bromo-quanosine 3', 5'-cyclic monophosphate [8-bromo-cGMP (10(-6) to 3 x 10(-6) M)]} signi ficantly inhibited TS-evoked nonadrenergic, noncholinergic relaxations in a dose-dependent manner. In contrast, vasoactive intestinal polype ptide (10(-8) M)-induced relaxations were not affected by SIN-1 or 8-b romo-cGMP. TS evoked a significant increase in H-3-citrulline formatio n, which was completely abolished by calcium-free medium, N-G-nitro-L- arginine methyl ester, (10(-4) M) and tetrodotoxin (10(-6) M). 3H-citr ulline formation evoked by TS was significantly inhibited by SIN-1 (10 (-7) to 10(-5) M) and 8-bromo-cGMP (10(-7) to 10(-5) M) in a dose-depe ndent manner. The inhibitory effect of SIN-I was partially prevented b y 1H-[1,2,4]oxadiazolo[3,4-a]quinoxalin-1-one (10(-5) M), a guanylate cyclase inhibitor. We conclude that NO synthesis in the gastric myente ric plexus is negatively regulated by NO and cGMP. This suggests an au toregulatory feedback mechanism of NO synthesis in the gastric myenter ic plexus.