Vincens M, Dartois E, Moyse E, Haour F, Fillion G
Université Paris VII, Hopital Lariboisiere, France.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Apr;351(4):356-62. doi: 10.1007/BF00169075.
Using quantitative autoradiography, we have studied the distribution of the [35S]-TBPS binding sites of the GABA-A receptor complex in various structures of the rat brain. High densities of binding sites were observed in layer IV of the cerebral cortex, in the globus pallidus, and in the thalamus. Intermediate densities of binding sites were observed in superficial and deep layers of the cerebral cortex, in the dentate gyrus and in the hippocampus. For all of these structures, the interactions of 3 alpha-OH-5 alpha-pregnan-20-one (3 alpha 5 alpha P), pregnenolone sulfate (PS), and pentobarbital with [35S]-TBPS binding, in the presence or the absence of GABA were studied. In the absence of GABA, IC50 values for the inhibition of [35S]-TBPS binding were 10(-6) M for 3 alpha 5 alpha P and 10(-4) M for PS and pentobarbital in all of the brain regions studied. In the presence of GABA (5 x 10(-6) M), IC50 values were decreased by one order of magnitude for 3 alpha 5 alpha P, PS, and pentobarbital in all structures studied except layer IV of the cortex, where the IC50 value for PS was more markedly decreased (up to two orders of magnitude). By contrast, IC50 values for picrotoxin and TBPS to inhibit [35S]-TBPS binding were 10(-7) M and 10(-8) M, respectively, in the presence or absence of GABA.
我们运用定量放射自显影技术，研究了大鼠脑不同结构中GABA - A受体复合物的[35S] - TBPS结合位点的分布情况。在大脑皮层的IV层、苍白球和丘脑中观察到高密度的结合位点。在大脑皮层的浅层和深层、齿状回和海马体中观察到中等密度的结合位点。对于所有这些结构，研究了在存在或不存在GABA的情况下，3α - OH - 5α - 孕烷 - 20 - 酮（3α5αP）、硫酸孕烯醇酮（PS）和戊巴比妥与[35S] - TBPS结合的相互作用。在不存在GABA的情况下，在所研究的所有脑区中，抑制[35S] - TBPS结合的IC50值对于3α5αP为10(-6) M，对于PS和戊巴比妥为10(-4) M。在存在GABA（5×10(-6) M）的情况下，除皮层IV层外，在所有研究的结构中，3α5αP、PS和戊巴比妥的IC50值均降低了一个数量级，在皮层IV层中，PS的IC50值降低更为显著（高达两个数量级）。相比之下，在存在或不存在GABA的情况下，苦味毒和TBPS抑制[35S] - TBPS结合的IC50值分别为10(-7) M和10(-8) M。
