Role of beta-adrenergic receptors in catecholamine-induced desensitization of adenylate cyclase in human astrocytoma cells

Johnson, G.L.; Wolfe, B.B.; Harden, T.K.; Molinoff, P.B.; Perkins, J.P.

Journal of Biological Chemistry 253(5): 1472-1480


ISSN/ISBN: 0021-9258
PMID: 203594
Accession: 068523927

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EH118MG human astrocytoma cells respond to catecholamines and to prostaglandin E1 (PGE1) with a rapid but transient accumulation of intracellular ciodohydroxybenzylpindolol even though a 50-60% loss in responsiveness to isoproternol was observed. The catecholamine-induced desensitization observed with intact cells also was demonstrated in broken cell preparations. The degree of desensitization (35-50%) was much less after homogenization. No change in catecholamine-sensitive adenylate cyclase activity, measured in homogenates, was demonstrated after exposure of intact cells to PGE1, even though a marked loss of responsiveness (50-60%) was observed on subsequent exposure of the intact cells to isoproterenol. Changes in adenylate cyclase activity that occur after exposure of cells to specific hormones might involve both changes in receptor number and alterations of the adenylate cyclase system distal to the hormone-receptor interaction. The nonspecific component of desensitization was rapidly reversible upon homogenization, did not involve a change in receptor number and was probably mediated by cAMP.