Regulation of Adenylate Cyclase of Neuroblastoma x Glioma Hybrid Cells by wAdrenergic Receptors I. INHIBITION OF ADENYLATE CYCLASE MEDIATED BY LY RECEPTORS*

(-)-Norepinephrine and other catecholamines inhibit basal and prostaglandin El-stimulated adenylate cyclase activities by 35 to 60% in homogenates of NG10815 neuroblastoma x glioma hybrid cells and markedly reduce adenosine 3’:5’-monophosphate levels of intact cells, but do not affect guanosine 3’:5’-monophosphate levels. The specificity of the NGlOS-15 receptor for ligands is that of an (Y receptor, possibly a presynaptic (~2 receptor. The inhibition of adenylate cyclase by norepinephrine is reversed by (Y receptor antagonists such as dihydroergotamine or phentolamine, but not by the p receptor antagonist propranolol. The effect of norepinephrine on adenylate cyclase activity initially is dependent on GTP; half-maximal inhibition of enzyme activity by norepinephrine is obtained with 0.2 pM GTP. The inhibition of adenylate cyclase activity by norepinephrine is reduced by 10 mM NaF and is abolished by 0.05 mM guanyl-5’-yl imidodiphosphate. Inhibitions of NGlOS-15 adenylate cyclase mediated by (Y receptors, opiate receptors, and muscarinic acetylcholine receptors are not additive; this suggests that the three species of receptors can be functionally coupled to the same adenylate cyclase molecules or molecules regulating the enzyme.