Roca D J, Schiller G D, Farb D H
Department of Anatomy and Cell Biology, State University of New York Health Science Center at Brooklyn 11203.
Mol Pharmacol. 1988 May;33(5):481-5.
Methylxanthines, such as caffeine and theophylline, are adenosine receptor antagonists that exert dramatic effects upon the behavior of vertebrate animals by increasing attentiveness, anxiety, and convulsive activity. Benzodiazepines, such as flunitrazepam, generally exert behavioral effects that are opposite to those of methylxanthines. We report the finding that chronic exposure of embryonic brain neurons to caffeine or theophylline reduces the ability of gamma-aminobutyric acid (GABA) to potentiate the binding of [3H]flunitrazepam to the GABA/benzodiazepine receptor. This theophylline-induced "uncoupling" of GABA- and benzodiazepine-binding site allosteric interactions is blocked by chloroadenosine, an adenosine receptor agonist, indicating that the chronic effects of theophylline are mediated by a site that resembles an adenosine receptor. We speculate that adverse central nervous system effects of long-term exposure to methylxanthines such as in caffeine-containing beverages or theophylline-containing medications may be exerted by a cell-mediated modification of the GABAA receptor.
甲基黄嘌呤，如咖啡因和茶碱，是腺苷受体拮抗剂，通过提高注意力、增加焦虑和引发惊厥活动，对脊椎动物的行为产生显著影响。苯二氮䓬类药物，如氟硝西泮，通常产生与甲基黄嘌呤相反的行为效应。我们报告了这样一个发现：胚胎脑神经元长期暴露于咖啡因或茶碱会降低γ-氨基丁酸（GABA）增强[3H]氟硝西泮与GABA/苯二氮䓬受体结合的能力。茶碱诱导的GABA和苯二氮䓬结合位点变构相互作用的“解偶联”被腺苷受体激动剂氯腺苷阻断，这表明茶碱的长期效应是由一个类似于腺苷受体的位点介导的。我们推测，长期接触甲基黄嘌呤，如含咖啡因的饮料或含茶碱的药物，对中枢神经系统产生的不良影响可能是通过细胞介导的GABAA受体修饰来实现的。
