'GABA shift' in vivo: enhancement of benzodiazepine binding in vivo by modulation of endogenous GABA.
'GABA shift' in vivo: enhancement of benzodiazepine binding in vivo by modulation of endogenous GABA.
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体内“GABA 转变”：通过调节内源性 GABA 增强体内苯二氮卓结合。
DOI：
10.1016/0014-2999(88)90461-x
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发表时间：
1988
影响因子：
5
通讯作者：
R. Shader
中科院分区：
文献类型：
--
作者：
L. G. Miller;D. Greenblatt;J. Barnhill;Warren R. Summer;R. Shader
γ-氨基丁酸（GABA）及其类似物对苯并二氮卓因结合的增强作用已在脑细胞膜制备物中详细描述，但在体内制备物（如用GABA调节剂处理的组织切片或动物）中的结果相互矛盾。据报道，这种“GABA移位”在体外对苯二氮卓类受体具有激动剂作用的化合物有报道，但拮抗剂没有。我们通过苯二氮卓类拮抗剂[3 H]Ro 15-1788的特异性摄取来确定内源性GABA调节剂对体内苯二氮卓类受体结合的影响。氨基氧乙酸（AOAA）处理后4 h，丙戊酸处理后0.5h，皮质、小脑、下丘脑、海马和桥-髓质，γ-乙烯基-GABA处理后6 h，皮质、小脑、下丘脑和海马的放射性配体摄取明显增加。皮质GABA浓度在这些点的每一个增加，作为突触体GABA浓度在以前的研究。相反，γ-乙烯基-GABA处理后12和24 h，未观察到放射性配体摄取或GABA浓度的变化。结合的增加似乎是由于受体的表观亲和力增加，而不是受体数量的变化。这些数据表明，苯二氮卓类拮抗剂的结合在体内经历了类似于在体外用激动剂观察到的GABA移位。
The enhancement of benzodiazeoine binding by γ-aminobutyric acid (GABA) and its analogues has been described in detail in brain membrane preparations, but results in in vivo preparations such as tissue slices or animals treated with GABA modulators are conflicting. This ‘GABA shift’ in vitro has been reported for compounds with agonist effects at the benzodiazepine receptor but not for antagonists. We examined the effects of modulators of endogenous GABA on benzodiazepine receptor binding in vivo as determined by specific uptake of the benzodiazepine antagonist [3H]Ro 15–1788. Enhancement of radioligand uptake was observed in cortex, hypothalamus, hippocampus and pons-medulla 4 h after treatment with aminooxyacetic acid (AOAA), in cortex, cerebellum, hypothalamus, hippocampus and pons-medulla 0.5 h after treatment with valproic acid, and in cortex, cerebellum, hypothalamus and hippocampus 6 h after treatment with γ-vinyl-GABA. Cortex GABA concentrations were increased at each of these points, as were synaptosomal GABA concentrations in prior studies. In contrast, no changes in radioligand uptake or GABA concentrations were observed 12 and 24 h after γ-vinyl-GABA treatment. Increases in binding appeared to be due to increased apparent affinity at the receptor rather than a change in receptor number. These data indicate that binding of a benzodiazepine antagonist undergoes a GABA shift in vivo analogous to that observed with agonists in vitro.
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苯二氮卓受体与 γ-氨基丁酸 (GABA) 受体亚群偶联：来自定量放射自显影研究的证据。
DOI：
--
发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Unnerstall,JR;Kuhar,MJ;Niehoff,DL;Palacios,JM
通讯作者：
Palacios,JM
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影响因子：
2.5
作者：
Miller,LG;Friedman,H;Greenblatt,DJ
通讯作者：
Greenblatt,DJ
苯二氮卓受体在体内与 [3H]-Ro 15-1788 结合。
影响因子：
6.1
作者：
Goeders,NE;Kuhar,MJ
通讯作者：
Kuhar,MJ
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DOI：
--
发表时间：
1987
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Miller,LG;Greenblatt,DJ;Paul,SM;Shader,RI
通讯作者：
Shader,RI