Li C, Peoples R W, Weight F F
Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8115, USA.
Br J Pharmacol. 1998 Jan;123(1):1-3. doi: 10.1038/sj.bjp.0701599.
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.
乙醇通过以明显竞争性的方式将ATP浓度-反应曲线向右移动来抑制神经元P2X嘌呤受体。然而，其潜在机制尚未确定。我们研究了乙醇对牛蛙背根神经节神经元中ATP激活电流的激活和失活时间常数的影响。乙醇降低了ATP门控离子通道的失活时间常数，而不影响激活时间常数。这些观察结果与乙醇的竞争性抑制机制不一致，但可能是由于乙醇的变构作用降低了表观激动剂亲和力来解释。这代表了乙醇对神经递质门控离子通道的一种新作用机制。
