Rägo L, Kiivet R A, Harro J, Pŏld M
Department of Pharmacology, Tartu University, Estonia, USSR.
Pharmacol Biochem Behav. 1989 Apr;32(4):879-83. doi: 10.1016/0091-3057(89)90052-x.
Central- and peripheral-type benzodiazepine (BD) receptors were labelled either by 3H-flunitrazepam or 3H-Ro 5-4864 in vitro after stress and in vivo administration of GABAA and GABAB agonists. A significant increase in the density of cerebral cortex and kidney BD binding sites was observed in rats after forced swimming stress. Similar changes in both type of BD receptors were also followed when naive (stressed) and handling-habituated (unstressed) rats were used. Stress in both models was unable to change the affinity of BD receptors in cerebral cortex, but significantly lowered it in kidneys. Acute treatment of rats with muscimol (1.5 mg/kg) or (-)baclofen (5 mg/kg) resulted in marked increase in the affinity of BD binding not only in cerebral cortex but also in kidneys. After (-)baclofen treatment the number of BD binding sites was lowered in the structures studied. In a separate study mice selected according to their behavioral response to (-)baclofen (1 mg/kg) were studied. Two weeks after the selection it appeared that baclofen responders were behaviorally more "anxious" than baclofen nonresponders. The number of BD binding sites was reduced in cerebral cortex, cerebellum, heart and kidneys in baclofen responders as compared to baclofen nonresponders. In several cases the changes in peripheral BD binding sites were even more pronounced than those in central ones. The data presented here evidence that peripheral- and central-type BD receptors are regulated similarly by GABA and some models of stress. The physiological mechanisms involved in similar regulation of central- and peripheral-type BD receptors are yet unknown.
在应激以及体内给予GABAA和GABAB激动剂后，采用3H-氟硝西泮或3H-Ro 5-4864在体外对中枢型和外周型苯二氮䓬（BD）受体进行标记。在强迫游泳应激后，大鼠大脑皮质和肾脏BD结合位点的密度显著增加。当使用未处理（应激）和习惯处理（未应激）的大鼠时，两种类型的BD受体也出现了类似变化。两种模型中的应激均无法改变大脑皮质中BD受体的亲和力，但可显著降低肾脏中BD受体的亲和力。用蝇蕈醇（1.5mg/kg）或（-）巴氯芬（5mg/kg）对大鼠进行急性处理，不仅可使大脑皮质，还可使肾脏中BD结合的亲和力显著增加。在（-）巴氯芬处理后，所研究结构中BD结合位点的数量减少。在另一项研究中，对根据其对（-）巴氯芬（1mg/kg）的行为反应选择的小鼠进行了研究。选择两周后，发现对巴氯芬有反应的小鼠在行为上比无反应的小鼠更“焦虑”。与对巴氯芬无反应的小鼠相比，对巴氯芬有反应的小鼠大脑皮质、小脑、心脏和肾脏中BD结合位点的数量减少。在某些情况下，外周BD结合位点的变化甚至比中枢的变化更明显。此处提供的数据证明，外周型和中枢型BD受体受GABA和某些应激模型的调节方式相似。中枢型和外周型BD受体类似调节所涉及的生理机制尚不清楚。
