Ruano D, Araujo F, Bentareha R, Vitorica J
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Brain Res. 1996 Oct 28;738(1):103-8. doi: 10.1016/0006-8993(96)00764-0.
In the present communication we have investigated the pharmacological properties of the GABAA receptor from adult (3 months old) and aged (24 months old) Wistar rat prefrontal cortex. The prefrontal cortex is implicated in cognitive functions and stress and both processes seem to be altered during aging. These changes could be mediated by modifications in the GABAA receptor properties. Our results indicated the absence of generalized age-related modifications on the pharmacological properties of the GABAA receptor from prefrontal cortical membranes. Saturation experiments using the non-selective benzodiazepine [3H]flunitrazepam revealed that neither the Kd values or the Bmax were modified during aging. Moreover, Cl 218 872 displacement of [3H]flunitrazepam showed no age-related modifications on either the Kis or the relative proportion between the Type I and Type II benzodiazepine binding sites. Therefore, the benzodiazepine binding sites are well preserved in aged prefrontal cortex. On the other hand, saturation experiments using the GABA agonist [3H]muscimol demonstrated in the Bmax of the low affinity [3H]muscimol binding sites in aged rats (4.3 +/- 0.8 pmol/mg protein vs. 2.3 +/- 0.2 pmol/mg protein in adult and aged rats, respectively). However, no age-dependent modifications were observed in the allosteric interaction between GABA and benzodiazepine binding sites. These results demonstrate that the benzodiazepine binding sites and the GABA binding sites of the GABAA receptor complex from rat prefrontal cortical membranes are differentially affected by the aging process.
在本报告中，我们研究了成年（3个月大）和老年（24个月大）Wistar大鼠前额叶皮质中GABAA受体的药理学特性。前额叶皮质与认知功能和应激有关，而这两个过程在衰老过程中似乎都会发生改变。这些变化可能是由GABAA受体特性的改变介导的。我们的结果表明，前额叶皮质膜中GABAA受体的药理学特性不存在与年龄相关的普遍改变。使用非选择性苯二氮䓬类药物[3H]氟硝西泮进行的饱和实验表明，衰老过程中Kd值和Bmax均未改变。此外，[3H]氟硝西泮的Cl 218 872置换显示，I型和II型苯二氮䓬类结合位点的Kis或相对比例均不存在与年龄相关的改变。因此，苯二氮䓬类结合位点在老年前额叶皮质中保存完好。另一方面，使用GABA激动剂[3H]蝇蕈醇进行的饱和实验表明，老年大鼠中低亲和力[3H]蝇蕈醇结合位点的Bmax有所增加（成年和老年大鼠分别为4.3±0.8 pmol/mg蛋白和2.3±0.2 pmol/mg蛋白）。然而，未观察到GABA与苯二氮䓬类结合位点之间的变构相互作用存在年龄依赖性改变。这些结果表明，大鼠前额叶皮质膜中GABAA受体复合物的苯二氮䓬类结合位点和GABA结合位点受衰老过程的影响不同。
