Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade
Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade
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DOI：
10.1016/s0028-3908(03)00254-5
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发表时间：
2003-12-01
影响因子：
4.7
通讯作者：
Vaugeois, JM
中科院分区：
文献类型：
--
作者：
El Yacoubi, M;Ledent, C;Vaugeois, JM
腺苷A（2A）受体在乙醇催眠作用中的作用在小鼠中进行了评估。急性乙醇给药后，A（2A）受体缺陷型小鼠（A（2A）R KO）的翻正反射丧失持续时间短于野生型小鼠（A（2A）R WT），而两种表型之间的体温下降没有差异。相反，戊巴比妥给药后，A（2A）R KO小鼠的战斗反射丧失持续时间比对照组延长。腺苷摄取抑制剂双嘧达莫增加了CD 1小鼠和A（2A）R WT小鼠乙醇给药后观察到的睡眠时间，但在A（2A）R KO小鼠中未观察到。与选择性A（1）受体拮抗剂DPCPX不同，选择性A（2A）受体拮抗剂SCH 58261缩短了乙醇诱导的翻正反射丧失的持续时间，从而模拟缺陷小鼠中缺乏受体的情况。最后，非选择性腺苷受体拮抗剂咖啡因（25 mg/kg）减少了乙醇诱导的催眠作用。这些结果表明，A（2A）受体的激活，随后的细胞外腺苷水平的增加引起的管理高剂量的乙醇在其催眠作用中发挥作用。因此，A（2A）受体拮抗剂可能是用于缓解乙基昏迷的有用治疗剂。(C)2003年爱思唯尔有限公司保留所有战斗。
The role of the adenosine A(2A) receptor in the hypnotic effects of ethanol was assessed in mice. The duration of the loss of righting reflex following acute ethanol administration was shorter for A(2A) receptor-deficient mice (A(2A)R KO) than for wild-type mice (A(2A)R WT), whereas the fall in body temperature was not different between the two phenotypes. In contrast, the duration of the loss of fighting reflex was increased in A(2A)R KO mice versus controls after administration of pentobarbital. Dipyridamole, an inhibitor of adenosine uptake, increased the sleep time observed following administration of ethanol in CD1 mice and in A(2A)R WT but not in A(2A)R KO mice. SCH 58261, a selective A(2A) receptor antagonist, unlike DPCPX, a selective A(1) receptor antagonist, shortened the duration of the loss of righting reflex induced by ethanol, thus mimicking the lack of receptor in deficient mice. Finally, the non-selective adenosine receptor antagonist caffeine (25 mg/kg) reduced ethanol-induced hypnotic effects. These results indicate that the activation of A(2A) receptors that follows an increase in extracellular adenosine levels caused by the administration of high doses of ethanol plays a role in its hypnotic effects. Thus, A(2A) receptor antagonists may be useful therapeutic agents for alleviating ethylic coma. (C) 2003 Elsevier Ltd. All fights reserved.