In vitro maturation of the rat reticulocyte beta-adrenoceptor adenylate cyclase system

Reticulocytes but not mature erythrocytes are equipped with a functional beta-adrenergic system characterizing cells which are under adrenergic control. We have followed the decline of beta-adrenergic functions in a defined, phenylhydrazine-induced population of rat reticulocytes during maturation under cell culture conditions in vitro. beta-Agonist or forskolin-stimulated cyclic 3',5'-AMP (cAMP) formation decreased by 35 +/- 5% within 18 h and by 75 +/- 7% within 5 days. Regulatory control, i.e. the desensitization after chronic agonist exposure was observed at least for the first 18 h of incubation. The protein components of the system (receptors, nucleotide binding protein (N-protein), cyclase) seem to survive longer than 5 days. Our results suggest that an impaired interaction between N-protein and adenylate cyclase may be the initial step in the inactivation of the beta-adrenergic system in reticulocytes.