Unoccupied beta-adrenoceptor-induced adenylyl cyclase stimulation in turkey erythrocyte membranes.
The influence of beta-adrenoceptor ligands and a beta-adrenoceptor-derived peptide was studied on stimulation of adenylyl cyclase in membrane preparations of turkey erythrocytes. In the absence of receptor ligands, the hydrolysis-resistant GTP analogs, guanosine 5'-[gamma-thio]triphosphate and guanosine 5'-[beta,gamma-imino]triphosphate, caused a slow, time-dependent increase in adenylyl cyclase activity, which was accelerated and potentiated by the additional presence of the agonist, isoproterenol. In contrast, the beta-adrenoceptor antagonists, propranolol and pindolol, almost completely prevented stimulation of adenylyl cyclase by the GTP analogs alone, i.e. in the absence of an agonist, in a concentration-dependent and stereo-selective manner. This antagonist action was mimicked by a peptide corresponding to the second cytoplasmic loop of the turkey erythrocyte beta-adrenoceptor. On the other hand, GTP analog-preactivated cyclase activity and enzyme stimulation by fluoride and forskolin were not or only slightly reduced by beta-adrenoceptor antagonists. The data presented suggest that in turkey erythrocyte membranes agonist-free beta-adrenoceptors can cause significant Gs protein and subsequent adenylyl cyclase activation, and that this unoccupied receptor action can be blocked by beta-adrenoceptor antagonists, thus exhibiting by themselves a negative intrinsic activity.
Institut für Pharmakologie, Universität GH Essen, Germany.
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Götze
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Jakobs
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation; D004910:Erythrocyte Membrane / Q000201:enzymology*; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014422:Turkeys
D011943:Receptors, Adrenergic, beta; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011433:Propranolol; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases