Corda M G, Giorgi O, Longoni B, Ongini E, Pesce G, Cruciani R, Biggio G
Department of Experimental Biology, University of Cagliari, Italy.
Eur J Pharmacol. 1989 Oct 10;169(2-3):205-13. doi: 10.1016/0014-2999(89)90017-4.
The interaction between GABAA receptors and benzodiazepine (BZD) recognition site subtypes in the spinal cord of the rat was investigated. Computer analysis of displacement curves for [3H]flunitrazepam [( 3H]FNT) binding by 2-oxo-quazepam (2OXOQ) indicated the presence of two subtypes of BZD recognition sites in this region. Type I sites accounted for approximately 25% of the total number of BZD recognition sites, the remainder being Type II sites. A similar proportion of Type I and Type II sites was obtained by Scatchard analysis of the saturation curves for [3H]FNT, [3H]2OXOQ and [3H]ethyl-beta-carboline-3-carboxylate [( 3H]beta CCE) binding. The in vitro addition of GABA (10(-8)-10(-4) M) to spinal cord membrane preparations produced an increase in the binding of [3H]FNT and [3H]2OXOQ. The maximal enhancement produced by GABA was 50 and 82% above control values for [3H]FNT and [3H]2OXOQ, respectively. In contrast, GABA stimulated both [3H]FNT and [3H]2OXOQ binding in the cerebellum to a similar extent. We also evaluated the effects of different ligands for BZD recognition sites on the binding of [3H]GABA to spinal cord membranes, as compared with brain areas containing a higher proportion ( greater than 30%) of Type I sites. Diazepam, quazepam and the beta-carboline, ZK 93423, enhanced the specific binding of [3H]GABA in a concentration-dependent manner (10(-7)-10(-5) M) in the cerebral cortex and hippocampus but not in the spinal cord and cerebellum. These results indicate that there is a regional variation in the interaction between GABA and BZD recognition sites in the central nervous system.
研究了大鼠脊髓中γ-氨基丁酸A（GABAA）受体与苯二氮䓬（BZD）识别位点亚型之间的相互作用。通过计算机分析2-氧代夸西泮（2OXOQ）对[3H]氟硝西泮[（3H）FNT]结合的置换曲线，表明该区域存在两种BZD识别位点亚型。I型位点约占BZD识别位点总数的25%，其余为II型位点。通过对[3H]FNT、[3H]2OXOQ和[3H]乙基-β-咔啉-3-羧酸酯[（3H）βCCE]结合的饱和曲线进行Scatchard分析，得到了相似比例的I型和II型位点。在脊髓膜制剂中体外添加γ-氨基丁酸（GABA，10^(-8)-10^(-4)M）可使[3H]FNT和[3H] OXOQ的结合增加。GABA产生的最大增强分别比[3H]FNT和[3H]2OXOQ的对照值高50%和82%。相比之下，GABA对小脑[3H]FNT和[3H]2OXOQ结合的刺激程度相似。我们还评估了与含有较高比例（大于30%）I型位点的脑区相比，不同BZD识别位点配体对[3H]GABA与脊髓膜结合的影响。地西泮、夸西泮和β-咔啉ZK 93423在大脑皮层和海马体中以浓度依赖性方式（10^(-7)-10^(-5)M）增强[3H]GABA的特异性结合，但在脊髓和小脑中无此作用。这些结果表明，中枢神经系统中GABA与BZD识别位点之间的相互作用存在区域差异。
