Spiegel A M, Brown E M, Fedak S A, Woodard C J, Aurbach G D
J Cyclic Nucleotide Res. 1976;2(1):47-56.
Turkey erythrocyte membranes contain beta-adrenergic-coupled adenylate cyclase systems that are modulated by guanine nucleotides. Incubation of membranes with Gpp (NH) p plus isoproterenol led to a persistently activated state ("holocatalytic state") of adenylate cyclase independent of agonist. Formation of this holocatalytic state was inhibited by conditions (4 degrees) or by compounds (e.g., GTP EDTA) that prevented Gpp (NH) p binding or that prevented binding of isoproterenol (e.g., propranolol). None of these agents, however, reduced activity of this activated state once it had been formed. The holocatalytic state, even though resistant to inhibition by propranolol, showed no change in receptor affinity or number of sites as determined by binding of 125I-HYP, a high affinity beta-adrenergic antagonist. Formation of the holocatalytic state, therefore, involves a modification of the adenylate cyclase system distal to the hormone receptor complex.
