Identification and persistence of beta adrenergic receptors during maturation of the rat reticulocyte
Bilezikian, J.P.; Spiegel, A.M.; Brown, E.M.; Aurbach, G.D.
Molecular Pharmacology 13(5): 775-785
1977
ISSN/ISBN: 0026-895X PMID: 197393 Document Number: 113537
Rat erythrocytes and reticulocytes were studied in relation to their responsiveness to .beta.-adrenergic catecholamines. Characteristics of .beta.-adrenergic receptors after induction of a maximal reticulocyte response with phenylhydrazine hydrochloride and after differentiation to morphologically mature erythrocytes were compared and correlated with concomitant changes in catecholamine-sensitive adenylate cyclase activity. Membranes from a population of 90% reticulocytes contain 25 .times. more adenylate cyclase activity than membranes from erythrocytes (5% reticulocytes). Potencies of a series of agonists and antagonists define this activity as .beta.-adrenergic. Adenylate cyclase activity varies directly with the reticulocyte percentage. Iodohydroxybenzylpindolol, a potent .beta.-adrenergic inhibitor that has been used successfully to detect .beta.-receptors, bound to sites in control and reticulocyte membranes with high affinity (Kd = 0.2 nM), low capacity and stereospecificity. Adrenergic compounds that stimulate or inhibit adenylate cyclase bound to the .beta.-receptor over a similar concentration range. Control erythrocytes from untreated rats and erythrocytes formed after reticulocytes were allowed to mature contain approximately half the receptors of reticulocytes. Characteristics of the .beta.-receptor from reticulocytes and mature erythrocytes are indistinguishable. Catecholamine-sensitive adenylate cyclase is rapidly lost as the reticulocyte matures, but significant binding activity persists. The .beta.-receptor may become uncoupled from the catalytic unit of adenylate cyclase during differentiation. .beta.-Adrenergic catecholamines may play a role in erythroid differentiation.