Abstract
Rat erythrocytes and reticulocytes have been studied in relation to their responsiveness to beta adrenergic catecholamines. The 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). The 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, binds to sites in both control and reticulocyte membranes with high affinity (KD = 0.2 nM), low capacity, and stereospecificity. Adrenergic compounds that stimulate or inhibit adenylate cyclase bind to the beta receptor over a similar concentration range. Control erythrocytes from untreated rats and erythrocytes formed after reticulocytes have been 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. These observations suggest that the beta receptor may become uncoupled from the catalytic unit of adenylate cyclase during differentiation. The results are also compatible with the hypothesis that beta adrenergic catecholamines play a role in erythroid differentiation.
ACKNOWLEDGMENTS The expert technical assistance of Mr. Donald Gammon and Mr. Charles Woodard is appreciated.
- Copyright © 1977 by Academic Press, Inc.
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