Freund R K, Palmer M R
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Alcohol Clin Exp Res. 1996 Apr;20(2):408-12. doi: 10.1111/j.1530-0277.1996.tb01661.x.
Previous studies in our laboratory indicated that electrophysiological responses of cerebellar Purkinje neurons to GABA were not routinely potentiated by ethanol (EtOH), and the potentiation was not large when it occurred. In the presence of beta-adrenergic agonists, such as isoproterenol, however, GABA inhibitions became sensitive to potentiation by EtOH in nearly every Purkinje neuron tested. beta-adrenergic receptor activation alone also modulates (potentiates) GABA responses on Purkinje neurons, and this has been reported to be mediated by a cAMP second messenger system. Herein, we report that the membrane-permeable cAMP analog, 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP), but not the membrane-impermeable cAMP, can also modulate GABA responses and that EtOH potentiates this facilitatory action of 8-Br-cAMP. These effects are not likely caused by adenosine receptor mechanisms, because this 8-bromoadenosine mediated modulation and sensitization was observed in the presence of systemic theophylline. These data suggest that the beta-adrenergic modulation and sensitization to EtOH of cerebellar Purkinje neuron GABA responses occur via a cAMP second messenger mechanism.
我们实验室之前的研究表明，小脑浦肯野神经元对γ-氨基丁酸（GABA）的电生理反应通常不会被乙醇（EtOH）增强，即便出现增强，幅度也不大。然而，在存在β-肾上腺素能激动剂（如异丙肾上腺素）的情况下，几乎在所测试的每一个浦肯野神经元中，GABA抑制作用变得对EtOH的增强敏感。单独的β-肾上腺素能受体激活也会调节（增强）浦肯野神经元上的GABA反应，据报道这是由环磷酸腺苷（cAMP）第二信使系统介导的。在此，我们报告膜通透性cAMP类似物8-溴腺苷-3',5'-环磷酸（8-Br-cAMP），而非膜不通透性cAMP，也能调节GABA反应，并且EtOH会增强8-Br-cAMP的这种促进作用。这些效应不太可能是由腺苷受体机制引起的，因为在存在全身应用茶碱的情况下观察到了这种8-溴腺苷介导的调节和致敏作用。这些数据表明，小脑浦肯野神经元GABA反应对β-肾上腺素能的调节和对EtOH的致敏作用是通过cAMP第二信使机制发生的。
