EVIDENCE FOR NO-CENTER-DOT REDOX FORM OF NITRIC-OXIDE AS NITRERGIC INHIBITORY NEUROTRANSMITTER IN GUT

A nitric oxide (NO)-like product of the L-arginine NO synthase pathway has been shown to be a major inhibitory neurotransmitter that is invo lved in the slow component of the inhibitory junction potential (IJP) elicited by stimulation of nonadrenergic, noncholinergic nerves. Howev er, the exact nature of the nitrergic transmitter, the role of cGMP, a nd the involvement of a potassium or a chloride conductance in the slo w IJP remain unresolved. We examined the effects of soluble guanylate cyclase inhibitors LY-83583 and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin- 1-one (ODQ), potassium-channel blockers and putative chloride-channel blockers diphenylamine-2-carboxylate (DPC) and niflumic acid (NFA) on the hyperpolarization elicited by an NO . donor, diethylenetriamine/NO adduct (DNO), NO in solution, and an NO+ donor, sodium nitroprusside (SNP), in the guinea pig ileal circular muscle. Effects of these block ers on purinergic (fast) and nitrergic (slow) IJP were also examined. DNO-induced hyperpolarization and nitrergic slow IJP were suppressed b y LY-83583 or ODQ and DPC or NFA but not by the potassium-channel bloc ker apamin. In contrast, hyperpolarization caused by SNP or solubilize d NO gas and purinergic fast IJP were antagonized by apamin but not by inhibitors of guanylate cyclase or chloride channels. These results d emonstrate biological differences in the actions of different redox st ates of NO and suggest that NO . is the nitrergic inhibitory neurotran smitter.