Ethanol inhibits nonadrenergic, noncholinergic neurotransmission in the anococcygeus muscle of the rat.
The anococcygeus muscle of the rat is innervated by both excitatory adrenergic and inhibitory nonadrenergic, noncholinergic (NANC) neurons. The transmitter released from NANC neurons appears to be nitric oxide or a related molecule. In vitro, acute administration of ethanol inhibited, in a dose-dependent manner, NANC-induced relaxation of anococcygeus muscle obtained from ethanol-naive animals. Two days of in vivo ethanol administration resulted in an increase in the maximal relaxation induced by stimulation of NANC neurons and in a significant shift to the right of the acute ethanol dose-response curve for inhibition of NANC relaxation. The sensitivity of the anococcygeus muscle to relaxation induced by the nitric oxide donors, acidified sodium nitrite or sodium nitroprusside, was not altered significantly by acute in vitro or chronic ethanol treatment 2 days in vivo. These data suggest that acutely administered in vitro ethanol inhibits the production of nitric oxide induced by stimulation of NANC neurons. Data further suggest that 2 days of ethanol administration in vivo produce an enhanced responsiveness of the NANC neurons to transmural stimulation and that this enhanced responsiveness accounts for the tolerance to the inhibition induced by the acutely administered ethanol in vitro.
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Department of Pharmacology, School of Medicine, University of Minnesota-Duluth 55812.
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004558:Electric Stimulation; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D009599:Nitroprusside; D009569:Nitric Oxide; D000431:Ethanol; D012977:Sodium Nitrite; D009638:Norepinephrine