Relationship of GABAa receptor heterogeneity to regional differences in drug response.
Relationship of GABAa receptor heterogeneity to regional differences in drug response.
复制标题
GABAa 受体异质性与药物反应区域差异的关系。
DOI：
10.1007/bf00972200
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发表时间：
1990
影响因子：
4.4
通讯作者：
Tallman,JF
中科院分区：
文献类型：
--
作者：
Gallager,DW;Tallman,JF
GABAa 受体的分子生物学方法使人们对该复合物的结构和药理学有了新的认识。已知GABAa复合物是由多个亚基组成的杂低聚物，其中含有GABA、苯二氮卓类药物和巴比妥酸盐的结合位点。这些亚基还包含细胞内激酶磷酸化的调节位点。 GABAa 受体复合物的各个亚基的表达似乎存在区域差异。分子异质性的功能意义尚不清楚，但预计区域差异可能导致药理学上不同的反应。对长期服用地西泮影响的研究清楚地描绘了这种区域差异。长期服用苯二氮卓类药物会导致中缝背侧对 GABA 的电生理作用不敏感，但黑质网状部的 GABA 接受神经元不会。这些数据与慢性苯二氮卓类暴露反应的区域异质性一致。希望通过了解GABAa受体异质性及其分子基础，我们可以改善苯二氮卓类药物现有的受体亚型特异性和药理学。
Molecular biological approaches to the GABAa receptor have resulted in new insights into the structure and pharmacology of this complex. It is known that the GABAa complex is a heterooligomer composed of multiple subunits which contain binding sites for the GABA, benzodiazepines and barbiturates. These subunits also contain regulatory sites for phosphorylation by intracellular kinases. There appear to be regional differences in the expression of the various subunits for the GABAa receptor complex. The functional significance of molecular heterogeneity is not yet known but it is expected that regional differences may result in pharmacologically diverse responses. Studies on the effects of chronic administration of diazepam have clearly delineated such regional differences. Chronic benzodiazepine administration results in the development of subsensitivity to the electrophysiological actions of GABA in the dorsal raphe, but not in GABA receptive neurons of the substantia nigra pars reticulata. Such data is consistent with regional heterogeneity in response to chronic benzodiazepine, exposure. It is hoped that by understanding GABAa receptor heterogeneity, and its molecular basis, we can improve the, existing receptor subtype specificity and pharmacology of the benzodiazepines.