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Desensitization of catecholamine-stimulated adenylate cyclase and down-regulation of beta-adrenergic receptors in rat glioma C6 cells. Role of cyclic AMP and protein synthesis.

Abstract：

:When exposed to the beta-agonist (-)-isoproterenol, rat glioma C6 cells exhibited a time-and concentration-dependent reduction in isoproterenol responsiveness (desensitization) and a loss of beta-adrenergic receptors (down-regulation). Other agents, such as dibutyryl cyclic AMP, isobutylmethylxanthine, and cholera toxin, all of which elevate intracellular cyclic AMP levels, also induced receptor down-regulation but at a much slower rate than isoproterenol. Loss of beta-receptors was detected with intact cells, cell lysates, and cell membranes. Receptor loss was accompanied by a reduction in isoproterenol-stimulated cyclic AMP production and adenylate cyclase activity. For a given amount of receptor loss, this reduction was much greater with isoproterenol than with other agents. In addition, the concentration of isoproterenol required for half-maximal stimulation of cyclic AMP production was increased in cells treated with isoproterenol but not with isobutylmethylxanthine or dibutyryl cyclic AMP. The affinity of beta-receptors for the agonist was also lower in membranes from cells treated with isoproterenol but not the other agents. Prior treatment of the cells with cycloheximide inhibited receptor loss by isoproterenol but did not prevent desensitization or reduced affinity of beta-receptors for the agonist. Cycloheximide also blocked the loss of receptors induced by dibutyryl cyclic AMP and, in addition, prevented a reduction in agonist-stimulated adenylate cyclase activity. We propose that desensitization is mediated in rat glioma C6 cells only by agonists and is not dependent on either cyclic AMP or protein synthesis. Down-regulation can be induced both by agonists and by cyclic AMP and does depend on protein synthesis. Thus, desensitization and down-regulation can occur independently.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Zaremba TG,Fishman PH

subject

Has Abstract

pub_date

1984-09-01 00:00:00

pages

206-13

issue

eissn

0026-895X

issn

1521-0111

journal_volume

pub_type

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Desensitization of catecholamine-stimulated adenylate cyclase and down-regulation of beta-adrenergic receptors in rat glioma C6 cells. Role of cyclic AMP and protein synthesis.