CGP 52432 - A NOVEL POTENT AND SELECTIVE GABA(B) AUTORECEPTOR ANTAGONIST IN RAT CEREBRAL-CORTEX
CGP 52432 - A NOVEL POTENT AND SELECTIVE GABA(B) AUTORECEPTOR ANTAGONIST IN RAT CEREBRAL-CORTEX
复制标题
DOI：
10.1016/0014-2999(93)90268-m
复制
发表时间：
1993-06-24
影响因子：
5
通讯作者：
RAITERI, M
中科院分区：
文献类型：
--
作者：
LANZA, M;FASSIO, A;RAITERI, M
如前所述，GABA（B）受体是异质性的。大鼠大脑皮质轴突终末存在三种不同的受体亚型，分别介导γ-氨基丁酸（GABA）、谷氨酸和生长抑素释放的抑制。我们研究了新型GABA（B）受体拮抗剂[3-[[（3，4-二氯苯基）甲基]氨基]丙基]（二乙氧基甲基）次膦酸（CGP 52432）对上述受体亚型的作用。CGP 52432可拮抗（-）-巴氯芬对K+诱发的大鼠皮层突触体释放GABA、谷氨酸或生长抑素的作用。药物对GABA自身受体的IC 50（0.085 μ M）分别比调节生长抑素和谷氨酸溢出的受体低35倍和100倍。在自身受体处，计算出的CGP 52432的pA 2为7.70，这使得该药物在该受体处的效力比法氯芬强约1000倍。CGP 52432的效力和选择性特征表明，该药物是迄今为止研究大鼠大脑皮层末端GABA（B）自身受体的最合适的工具。
As previously reported GABA(B) receptors are heterogeneous. Three pharmacologically distinct receptor subtypes mediating inhibition of gamma-aminobutyric acid (GABA), glutamate or somatostatin release, respectively, exist on axon terminals of rat cerebral cortex. We investigated the novel GABA(B) receptor antagonist, [3-[[(3,4-dichlorophenyl)methyl]amino]propyl](diethoxymethyl) phosphinic acid (CGP 52432), on the above receptor subtypes. The effects of (-)-baclofen on the K+-evoked release of GABA, glutamate or somatostatin from rat cortical synaptosomes were antagonized by CGP 52432. The IC50 of the drug at GABA autoreceptors (0.085 muM) was 35- and 100-fold lower than at the receptors regulating somatostatin and glutamate overflow, respectively. At the autoreceptor the calculated pA2 for CGP 52432 amounted to 7.70, which makes the drug about 1000-fold more potent than phaclofen at this receptor. The potency and selectivity characteristics of CGP 52432 indicate that the drug is by far the most appropriate tool to investigate the terminal GABA(B) autoreceptors of the rat cerebral cortex.