ENANTIOSELECTIVITY AT THE PHYSIOLOGICALLY ACTIVE GABA-A RECEPTOR
ENANTIOSELECTIVITY AT THE PHYSIOLOGICALLY ACTIVE GABA-A RECEPTOR
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DOI：
10.1016/0006-2952(91)90652-l
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发表时间：
1991-04-15
影响因子：
5.8
通讯作者：
HAJOS, F
中科院分区：
文献类型：
--
作者：
KARDOS, J;KOVACS, I;HAJOS, F
从大鼠脑皮质组织的一个亚组分，含有膜囊泡新鲜制备的蛋白酶抑制剂和抗氧化剂。 该制剂用于测量在30度生理盐溶液中二氢蝇蕈醇的（+）-（S）和（-）-（R）对映体对跨膜Cl-36-通量的刺激和对布库库林敏感性[H-3]蝇蕈醇结合的抑制。 结合的[H-3]蝇蕈醇的置换和Cl-36-通量的刺激出现在对映体的0.1-10 μ M浓度范围内，然而，通道门控需要相当高的浓度。 通道门控的对映体选择性程度、GABA（A）受体的脱敏和结合通过二氢蝇蕈醇对映体的浓度比[（-）-（R）]/[（+）-（S）]来估计，在相同的响应或置换水平下。 对于通道门控（6 +/-3）、受体结合（3 +/-2）和脱敏（无选择性）观察到不同的对映体选择性。 通道门控和受体结合的低浓度依赖性对映体选择性可以通过GABA（A）受体的脱敏和异质性来解释。
A subfraction of cortical tissue from rat brain, containing membrane vesicles was prepared freshly with added protease inhibitors and antioxidant. The preparation was used to measure stimulation of transmembrane Cl-36- flux and inhibition of bucuculline-sensitive [H-3] muscimol binding by (+)-(S) and (-)-(R) enantiomers of dihydromuscimol at 30-degrees in physiological salt solution. Displacement of bound [H-3]muscimol and stimulation of Cl-36- flux appeared in the 0.1-10-mu-M concentration range of the enantiomers, channel gating, however, required rather high concentrations. Degrees of enantioselectivity for channel gating, desensitization of and binding to GABA(A) receptors were estimated by the concentration ratios of dihydromuscimol enantiomers, [(-)-(R)]/[(+)-(S)], at the same level of response or displacement. Different enantioselectivities were observed for channel gating (6 +/- 3), receptor binding (3 +/- 2) and desensitization (no selectivity). The low and concentration-dependent enantioselectivities found for channel gating and receptor binding can be explained by desensitization and heterogeneity of GABA(A) receptors.