CYCLODIENE INSECTICIDES INHIBIT GABA-A RECEPTOR-REGULATED CHLORIDE TRANSPORT
CYCLODIENE INSECTICIDES INHIBIT GABA-A RECEPTOR-REGULATED CHLORIDE TRANSPORT
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DOI：
10.1016/0041-008x(87)90206-7
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发表时间：
1987-05-01
影响因子：
3.8
通讯作者：
ELDEFRAWI, AT
中科院分区：
文献类型：
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作者：
GANT, DB;ELDEFRAWI, ME;ELDEFRAWI, AT
通过 BABA 刺激 36Cl 流入膜微囊来测定大鼠脑中 GABAA 受体的功能。所测量的通量由 GABAA 受体激活引起的证据得到了蝇蕈醇在诱导 36Cl- 流入方面比 GABA 更高的效力的支持，希尔系数分别为 1.71 和 1.87，表明两个激动剂分子与每个受体结合。此外，GABA 诱导的 36Cl- 流入可被惊厥剂印海毒素和叔丁基二环硫代磷酸酯 (TBPS) 抑制，并且竞争性抑制剂 (+)-荷包牡丹碱比 (-)-荷包牡丹碱抑制 36Cl- 流入更有效。此外，用戊巴比妥或地西泮预温育膜增加了GABAA受体对GABA的亲和力，如通过相同GABA浓度诱导的36Cl流入增加而不增加最大36Cl流入来判断。 BABAA 受体脱敏，如 BABA 诱导的 36 Cl 流入的剂量依赖性减少所示，这是由于膜与 GABA 预孵育所致。七种环二烯抑制 GABA 诱导的 36Cl- 流入，硫丹 I 和异狄氏剂比其毒性较小的异构体硫丹 II 和狄氏剂更有效，七氯和艾氏剂的环氧化物（即狄氏剂）比其毒性较小的母体化合物更有效。这些环二烯对[35S]TBPS 与大鼠脑膜结合的抑制与其对 GABA 诱导的 36Cl- 流入的抑制之间存在良好的相关性 (r = 0.9)。
The function of GABAA receptors in rat brain was assayed by BABA stimulation of 36Cl-influx into membrane microsacs. The evidence that the measured flux resulted from GABAA receptor activation was supported by the higher potency of muscimol than of GABA in inducing 36Cl- influx with Hill coefficients of 1.71 and 1.87, respectively, suggesting that two agonist molecules were binding to each receptor. Also, the GABA-induced 36Cl- influx was inhibited by the convulsants pictrotoxinin and t-butylbicyclophosphorothionate (TBPS), and the competitive inhibitor (+)-becuculline was more potent than (-)-bicuculline in inhibiting this 36Cl- influx. Furthermore, preincubation of the membranes with pentobarbital or diazepam increased the GABAA receptor''s affinity for GABA as judged by the increased 36Cl- influx induced by the same GABA concentrations without increasing maximal 36Cl- influx. The BABAA receptor was desensitized as shown by the dose-dependent reduction in BABA-induced 36Cl- influx that resulted from preincubation of the membranes with GABA. Seven cyclodienes inhibited the GABA-induced 36Cl- influx, with endosulfan I and endrin being more potent than their less toxic isomers endosulfan II and dieldrin, and the epoxides of heptachlor and aldrin (i.e., dieldrin) were more potent than their less toxic parent compounds. There was good correlation (r = 0.9) between inhibition of [35S]TBPS binding to rat brain membranes by these cyclodienes and their inhibition of GABA-induced 36Cl- influx.