Yu Z F, Cheng G J, Hu B R
State Key Laboratory of Medical Neurobiology, Shanghai Medical University.
Sheng Li Xue Bao. 1997 Feb;49(1):25-30.
After preincubation of crude synaptic membranes (P2 membranes) with phorber ester (PMA) or GABAB receptor agonist baclofen (BAL), the rate of inhibition of BAL on basal adenylate cyclase (AC) activity and forskolin-stimulated AC activity significantly reduced (desensitized). This effect of BAL did not change after preincubation with forskolin suggesting that the desensitization mechanism of GABAB receptor coupled AC is related with activation of protein kinase C (PKC), but not with protein kinase A. It was further found that the equilibrium dissociation constant (Kd) of GABAB receptor was increased during desensitization. Our results suggest that PKC activation may cause some structural or conformational changes of GABAB receptor, resulting in an uncoupling from G protein and desensitization of GABAB receptor-coupled AC.
在用佛波酯（PMA）或GABAB受体激动剂巴氯芬（BAL）对粗制突触膜（P2膜）进行预孵育后，BAL对基础腺苷酸环化酶（AC）活性和福斯高林刺激的AC活性的抑制率显著降低（脱敏）。在用福斯高林预孵育后，BAL的这种作用没有改变，这表明GABAB受体偶联的AC的脱敏机制与蛋白激酶C（PKC）的激活有关，而与蛋白激酶A无关。进一步发现，在脱敏过程中GABAB受体的平衡解离常数（Kd）增加。我们的结果表明，PKC激活可能导致GABAB受体的一些结构或构象变化，导致与G蛋白解偶联以及GABAB受体偶联的AC脱敏。
