Ruano D, Cano J, Machado A, Vitorica J
Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, Spain.
J Pharmacol Exp Ther. 1991 Mar;256(3):902-8.
We have characterized the pharmacologic properties of the gamma-aminobutyric acid (GABAA)/benzodiazepine receptor complex in hippocampal membranes from 3-month- and 24-month-old Wistar rats. No major changes were found in [3H]flunitrazepam or [3H]muscimol binding parameters. Neither the dissociation constant(s) nor the Bmax for either ligand seemed to be modified during aging in hippocampus. Furthermore, the allosteric interaction between the barbiturates binding site and the GABA binding site, determined by pentobarbital stimulation of [3H] muscimol binding, remained unaltered. However, there was a significant increase with aging in the efficacy of the GABA-enhancement of [3H]flunitrazepam binding. On the other hand, we have also detected a significant increase in the proportion of type I benzodiazepine receptor in 24-month-old hippocampal membranes. We propose that the age-related increase in the efficacy of GABA-enhancement of [3H]flunitrazepam binding could be correlated with the increase in the proportion of type I benzodiazepine receptor. Based on these results it is tempting to speculate that the age-dependent modifications on the GABAA/benzodiazepine receptor might reflect an age-dependent neuronal degeneration of the hippocampus or the hippocampal formation.
我们已经对3月龄和24月龄Wistar大鼠海马膜中γ-氨基丁酸（GABAA）/苯二氮䓬受体复合物的药理学特性进行了表征。[3H]氟硝西泮或[3H]蝇蕈醇结合参数未发现重大变化。在海马老化过程中，两种配体的解离常数和Bmax似乎均未改变。此外，通过戊巴比妥对[3H]蝇蕈醇结合的刺激所确定的巴比妥类药物结合位点与GABA结合位点之间的变构相互作用保持不变。然而，随着年龄的增长，GABA增强[3H]氟硝西泮结合的效力显著增加。另一方面，我们还检测到24月龄海马膜中I型苯二氮䓬受体的比例显著增加。我们提出，GABA增强[3H]氟硝西泮结合效力的与年龄相关的增加可能与I型苯二氮䓬受体比例的增加相关。基于这些结果，很容易推测GABAA/苯二氮䓬受体的年龄依赖性修饰可能反映了海马或海马结构的年龄依赖性神经元变性。
