Evidence for NO. 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 involved in the slow component of the inhibitory junction potential (IJP) elicited by stimulation of nonadrenergic, noncholinergic nerves. However, the exact nature of the nitrergic transmitter, the role of cGMP, and the involvement of a potassium or a chloride conductance in the slow 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 blockers on purinergic (fast) and nitrergic (slow) IJP were also examined. DNO-induced hyperpolarization and nitrergic slow IJP were suppressed by LY-83583 or ODQ and DPC or NFA but not by the potassium-channel blocker apamin. In contrast, hyperpolarization caused by SNP or solubilized NO gas and purinergic fast IJP were antagonized by apamin but not by inhibitors of guanylate cyclase or chloride channels. These results demonstrate biological differences in the actions of different redox states of NO and suggest that NO. is the nitrergic inhibitory neurotransmitter.
Goyal
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Center for Swallowing and Motility Disorders, Brockton/West Roxbury Department of Veterans Affairs Medical Center, West Roxbury 02132; and Harvard Medical School, Boston, Massachusetts 02215, USA.
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D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation*; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000294:innervation*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009544:Niflumic Acid / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010084:Oxidation-Reduction; D026902:Potassium Channel Blockers; D011810:Quinoxalines / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000634:Aminoquinolines; D018118:Chloride Channels; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D062367:ortho-Aminobenzoates; D009599:Nitroprusside; D001030:Apamin; D009569:Nitric Oxide; D009544:Niflumic Acid; C041715:6-anilino-5,8-quinolinedione; C001209:fenamic acid; D006162:Guanylate Cyclase; D006152:Cyclic GMP