Studies on desensitization of GABAB receptor coupled adenylate cyclase

After preincubation of crude synaptic membranes (P2 membranes) with phorber ester (PMA) or GABAB receptor agonist baclofen (BAL), the rate of inhibition of BALon basal adenylate cyclase (AC) activity and forskolin-stimulated AC activity significantly reduced (desensitized). This effect of BAL did not change after preincubationwith forskolin suggesting that the desensitization mechanism of GABAB receptor coupledAC is related with activation of protein kinase C (PKC), but not with protein kinaseA. It was further found that the equilibrium dissociation constant (Kd) of GABAB receptor was increased during desensitization. Our results suggest that PKC activationmay cause some structural or conformational changes of GABAB receptor, resulting inan uncoupling from G protein and desensitization of GABAB receptor-coupled AC.