Ethanol-induced inhibition of a neuronal P2X purinoceptor by an allosteric mechanism.
Ethanol inhibits a neuronal P2X purinoceptor by shifting the ATP concentration-response curve to the right in an apparently competitive manner. However, the underlying mechanism has not been determined. We investigated the effects of ethanol on the activation and deactivation time constants for ATP-activated current in bullfrog dorsal root ganglion neurones. Ethanol decreased the time constant of deactivation of ATP-gated ion channels without affecting the time constant of activation. The observations are not consistent with a competitive mechanism of inhibition by ethanol, but may be explained by an allosteric action of ethanol to decrease apparent agonist affinity. This represents a novel mechanism of action of ethanol on a neurotransmitter-gated ion channel.
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Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8115, USA.
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D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D058919:Purinergic P2 Receptor Antagonists; D011892:Rana catesbeiana; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000737:chemistry
D002492:Central Nervous System Depressants; D007473:Ion Channels; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D000431:Ethanol; D000255:Adenosine Triphosphate