Potentiation of gamma-aminobutyric acid-mediated inhibition by isoproterenol in the cerebellar cortex: receptor specificity.
Potentiation of gamma-aminobutyric acid-mediated inhibition by isoproterenol in the cerebellar cortex: receptor specificity.
复制标题
小脑皮质中异丙肾上腺素增强γ-氨基丁酸介导的抑制作用：受体特异性。
DOI：
10.1016/0028-3908(90)90141-d
复制
发表时间：
1990
影响因子：
4.7
通讯作者：
Bickford-Wimer,PC
中科院分区：
文献类型：
--
作者：
Parfitt,KD;Hoffer,BJ;Bickford-Wimer,PC
大量的电生理数据支持去甲肾上腺素在中枢神经系统中的重要作用是调节其他递质系统的活动，特别是那些利用氨基酸神经递质的系统。许多研究人员已经观察到局部应用或突触释放的伽马氨基丁酸(GABA)对小脑浦肯野神经元的抑制反应的去甲肾上腺素能增强作用，他们认为β-肾上腺素能受体的激活在去甲肾上腺素(NE)的这种调制作用中起关键作用。已发现两种突触后GABA受体，分别称为A和B，并在大鼠小脑中发现这两种亚型。这项研究的目的是首先确定GABA受体的亚型(S)，该亚型负责介导局部应用的GABA在小脑皮质的抑制效应；其次，确定哪个亚型的GABA受体受到β-肾上腺素能输入的调节。本实验观察了乌拉坦麻醉大鼠小脑浦肯野神经元在局部应用异丙肾上腺素或去甲肾上腺素前、中、后对离子导入或加压GABA激动剂异古卡因、GABA激动剂巴氯芬或GABA本身的抑制反应。异古卡因，而不是巴氯芬，可引起持续的、剂量依赖性的浦肯野细胞放电抑制。在射血电流对自发放电频率没有影响的情况下，离子电泳法应用异丙肾上腺素可增强异古卡因的抑制作用。这些数据表明，介导GABA诱导的小脑浦肯野神经元抑制的是GABAA，而不是GABAB受体。此外，β-肾上腺素能激动剂对GABA功能的调节似乎涉及β-肾上腺素能输入与GABA受体复合体之间的相互作用。
A large body of electrophysiological data has supported the hypothesis that an important role of norepinephrine in the central nervous system is to modulate the actions of other transmitter systems, particularly those utilizing the amino acid neurotransmitters. Noradrenergic potentiation of inhibitory responses, induced by locally-applied or synaptically-released gamma-aminobutyric acid (GABA) on cerebellar Purkinje neurons, has been observed by a number of investigators, who have suggested that activation of beta-adrenergic receptors plays a critical role in mediating this modulatory effect of norepinephrine (NE). Two postsynaptic receptors for GABA, termed A and B, have been identified and both subtypes have been found in the cerebellum of the rat. The purposes of this investigation were first to identify the subtype(s) of GABA receptor responsible for mediating the inhibitory effects of locally-applied GABA in the cerebellar cortex and second to identify which subtype of GABA receptor is modulated by a beta-adrenergic input. Inhibitory responses of cerebellar Purkinje neurons, in urethane-anesthetized rats, to iontophoretic or pressure-applied isoguvacine, a selective GABAAagonist, to baclofen, a GABABagonist or to GABA itself, were examined before, during and after local application of isoproterenol or norepinephrine. Isoguvacine, but not baclofen, induced consistent and dose-dependent inhibition of the firing ofPurkinje cells. At ejection currents that had no effect on spontaneous firing rate, iontophoretically-applied isoproterenol potentiated isoguvacine-induced inhibition. These data suggest that GABAA, rather than GABABreceptors, mediate GABA-induced inhibitions of cerebellar Purkinje neurons. Moreover, it appears that the modulation of GABA function by beta adrenergic agonists involves an interaction between a beta-adrenergic input and the GABAAreceptor complex.