Backus K H, Kettenmann H, Schachner M
Department of Neurobiology, University of Heidelberg, Federal Republic of Germany.
Glia. 1988;1(2):132-40. doi: 10.1002/glia.440010205.
We have previously shown that cultured astrocytes from neonatal rat cerebral cortex are depolarized by GABA. The underlying ionic mechanism, activation of a Cl- conductance and responses to an agonist and antagonists were found to be similar to those of the neuronal GABAA receptor (Kettenmann et al.: Brain Research 404:1-9, 1987; Kettenmann and Schachner: Journal of Neuroscience 5:3295-3301, 1985). To characterize further the pharmacological properties of the GABA receptor we have tested the influence of pentobarbital and benzodiazepines on the GABA response. Pentobarbital potentiated and prolonged the GABA-induced depolarization and enhanced the velocity of the depolarization. Agonists of the neuronal benzodiazepine receptor, flunitrazepam, diazepam, and midazolam, increased the GABA-induced depolarization. As in neurons, an antagonist of the benzodiazepine receptor, Ro 15-1788, blocked the flunitrazepam-induced enhancement of the GABA response. In contrast to their effects on neurons, the inverse agonists Ro 22-7497 and DMCM increased the GABA-induced depolarization. The ligand of the putative peripheral benzodiazepine binding site, Ro 5-4864, did not show consistent effects on the GABA response. These studies confirm that cultured astrocytes express GABAA receptors. This receptor is similar to the neuronal GABAA receptor with regard to Cl- conductance and its pharmacological responses to muscimol, bicuculline, picrotoxin, pentobarbital, and benzodiazepine agonists and an antagonist, but it is different in its responses to inverse agonists of the benzodiazepine site. The physiological role of the glial GABAA receptor is at present unknown.
我们先前已表明，新生大鼠大脑皮层培养的星形胶质细胞会被γ-氨基丁酸（GABA）去极化。发现其潜在的离子机制、氯离子电导的激活以及对激动剂和拮抗剂的反应与神经元GABAA受体相似（凯滕曼等人：《脑研究》404:1 - 9，1987；凯滕曼和沙克纳：《神经科学杂志》5:3295 - 3301，1985）。为了进一步表征GABA受体的药理学特性，我们测试了戊巴比妥和苯二氮䓬对GABA反应的影响。戊巴比妥增强并延长了GABA诱导的去极化，并提高了去极化的速度。神经元苯二氮䓬受体激动剂氟硝西泮、地西泮和咪达唑仑增加了GABA诱导的去极化。与神经元情况一样，苯二氮䓬受体拮抗剂Ro 15 - 1788阻断了氟硝西泮诱导的GABA反应增强。与它们对神经元的作用相反，反向激动剂Ro 22 - 7497和DMCM增加了GABA诱导的去极化。假定的外周苯二氮䓬结合位点配体Ro 5 - 4864对GABA反应未表现出一致的影响。这些研究证实培养的星形胶质细胞表达GABAA受体。该受体在氯离子电导及其对蝇蕈醇、荷包牡丹碱、印防己毒素、戊巴比妥以及苯二氮䓬激动剂和拮抗剂的药理学反应方面与神经元GABAA受体相似，但在对苯二氮䓬位点反向激动剂的反应方面有所不同。目前尚不清楚胶质细胞GABAA受体的生理作用。
