The beta-adrenoceptor is precoupled to Gs in chicken erythrocyte membranes

In this study we seek to elucidate the mechanism of hormone-independent adenylate cyclase stimulation by Gpp(NH)p in chicken erythrocyte membranes, and the inhibition of this stimulation by propranolol. Membrane treatment with isoprenaline + GMP increased Gpp(NH)p stimulation to near maximal levels obtainable with isoprenaline + Gpp(NH)p], but reduced stimulation by NaF. The stimulation by Gpp(NH)p was stereoselectively inhibited by propranolol, but not by equal concentrations of the local anaesthetic lignocaine. Propranolol's inhibitory action was abolished following membrane treatment with isoprenaline/GMP. In contrast to its inhibition of Gpp(NH)p stimulation, propranolol did not alter Gpp(NH)p-mediated 3H-GDP release from membranes. The polyene antibiotic filipin, which uncouples receptor (R) from Gs, also abolished Gpp(NH)p stimulation and this effect was partly overcome by membrane treatment. These results are consistent with a model in which free R exists in equilibrium with precoupled R.Gs complexes in the absence of hormone. These complexes are activated by Gpp(NH)p and dissociated by antagonists. The existence of such complexes is a prerequisite for Gpp(NH)p stimulatory action.