GAMMA-AMINOBUTYRIC-ACID AND ALCOHOL ACTIONS - NEUROCHEMICAL STUDIES OF LONG SLEEP AND SHORT SLEEP MICE
GAMMA-AMINOBUTYRIC-ACID AND ALCOHOL ACTIONS - NEUROCHEMICAL STUDIES OF LONG SLEEP AND SHORT SLEEP MICE
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DOI：
10.1016/0024-3205(86)90324-3
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发表时间：
1986-11-24
期刊：
影响因子：
6.1
通讯作者：
HARRIS, RA
中科院分区：
文献类型：
--
作者：
ALLAN, AM;HARRIS, RA
乙醇和戊巴比妥对 GABA 受体-氯离子通道复合物的影响在选择的小鼠中进行了评估，这些小鼠对乙醇的催眠作用具有不同的敏感性（长睡眠和短睡眠线）。在来自小脑或前脑的膜囊泡悬浮液（微囊）中测量 36 Cl-流入、[ 35 S]叔丁基二环硫代磷酸酯（TBPS）和[ 3 H]蝇蕈醇结合。与 SS 小脑相比，蝇蕈醇被发现是 LS 小脑中 36 Cl-通量更有效的刺激剂，但在两个系中达到了相似的最大吸收水平。蝇蕈醇从小脑微囊中取代了[35S]TBPS（惊厥位点的配体），LS 小鼠对蝇蕈醇的这种作用也比 SS 小鼠更敏感。然而，高亲和力[3H]蝇蕈醇结合位点的数量或亲和力在各品系之间没有差异。生理相关浓度的乙醇（15-50 mM）增强了 LS 小脑中 36 Cl- 吸收的蝇蕈醇刺激，但对 SS 小脑没有影响。乙醇未能改变任一条线刺激的海马微囊的氯化物通量。无论大脑区域如何，LS 和 SS 系对蝇蕈醇刺激的氯化物吸收的戊巴比妥电位的反应相似。 LS 和 SS 小鼠在蝇蕈醇刺激的氯化物吸收以及 [35S]TBPS 结合的蝇蕈醇置换方面所表现出的差异为对 GABA 能药物的行为反应的线性差异提供了生化解释。此外，研究结果表明，乙醇催眠的遗传差异与 GABA 操作的氯离子通道对乙醇的敏感性差异有关。
Effects of ethanol and pentobarbital on the GABA receptor-chloride channel complex were evaluated in mice selected for differential sensitivity to the hypnotic effects of ethanol (long sleep and short sleep lines). 36Cl- influx, [35S]t-butylbicyclophosphorothionate (TBPS) and [3H]muscimol binding were measured in a membrane vesicle suspension (microsacs) from cerebellum or forebrain. Muscimol was found to be a more potent stimulator of 36Cl- flux in the LS cerebellum, as compared to the SS cerebellum, but a similar maximal level of uptake was achieved in the two lines. Muscimol displaced [35S]TBPS (a ligand for the convulsant site) from cerebellar microsacs, and LS mice were also more sensitive than SS mice to this action of muscimol. However, the number or affinity of high affinity [3H]muscimol binding sites did not differ between the lines. Physiologically relevant concentrations of ethanol (15-50 mM) potentiated muscimol stimulation of 36Cl- uptake in LS cerebellum but had no effect in SS cerebellum. Ethanol failed to alter stimulated chloride flux hippocampal microsacs from either line. Both the LS and SS lines responded similarly to pentobarbital potential of muscimol stimulated chloride uptake regardless of brain region. The demonstrated difference between the LS and SS mice in muscimol stimulated chloride uptake as well as in muscimol displacement of [35S]TBPS binding offers a biochemical explanation for the line differences in behavioral responses to GABAergic agents. Moreover, the findings suggest that genetic differences in ethanol hypnosis are related to differences in the sensitivity of GABA-operated chloride channels to ethanol.