Characterization of heterologous desensitization of rat reticulocyte adenylate cyclase system

Treatment of rat reticulocytes with isoproterenol caused about 50, 25, and 25% decreases in beta-adrenergic agonist-, fluoride-, and guanine nucleotide-stimulated adenylate cyclase activities, respectively. The desensitization was also induced by dibutyryl adenosine 3',5'-cyclic monophosphate (cyclic AMP) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) prevented the isoproterenol-induced desensitization, suggesting the involvement of cyclic AMP in the desensitization. Time course studies revealed that the desensitization to NaF-AlCl3 occurred faster than that to isoproterenol. Furthermore, the rate of the resensitization to NaF-AlCl3 by removal of isoproterenol was also faster than that to isoproterenol. Thus, it is likely that both guanine nucleotide-binding stimulatory regulatory protein, Ns, and beta-adrenergic receptor are sequentially involved in both desensitization and resensitization of the adenylate cyclase system in rat reticulocytes to isoproterenol.