Close reciprocal regulation of beta 1- and beta 2-adrenergic receptors by dexamethasone in C6 glioma cells: effects on catecholamine responsiveness

H Zhong and KP Minneman

Department of Pharmacology, Emory University Medical School, Atlanta, Georgia 30322.

We studied the regulation of beta-adrenergic receptor (AR) subtypes co- existing in rat C6 glioma cells to clarify the importance of subtype ratio in responses to catecholamines. Radioligand binding studies with [125I]-cyanopindolol showed that beta 1- and beta 2-ARs co-existed in this cell line in approximately an 80:20 ratio. Norepinephrine (NE) and epinephrine (EPI) were equally potent in increasing cAMP accumulation, consistent with a primarily beta 1-response, although both beta 1- and beta 2-components of the response could be isolated using selective agonists (NE and zinterol), and antagonists (CGP 20712A and ICI 118,551). Little or no evidence of beta 3-ARs could be found in this cell line. Treatment of cells with 500 nM dexamethasone (DEX) for 48 hr increased the proportion of beta 2-ARs (20 to 60%). However, a reciprocal decrease in beta 1-ARs resulted in no change in total beta- ARs. Studies on the time-(12 to 72 hr) and concentration- (5 nM to 5000 nM) dependence of DEX treatment showed that increases in beta 2-ARs were closely linked to decreases in beta 1-ARs with little or no change in total receptor density observed at any time or in any concentration studied. Treatment with DEX also increased beta 2- and decreased beta 1- mediated cAMP responses, but did not alter the response to the nonselective agonist, isoproterenol. Northern blot analysis showed a 2- to 3-fold increase in beta 2-AR mRNA, but no change in beta 1-AR mRNA, after exposure to 50 or 500 nM DEX for 48 hr. Surprisingly, after DEX treatment, NE and EPI were still equally potent in activating cAMP accumulation, although responses to the beta 2-selective agonist, zinterol, were increased. These studies show a close reciprocal regulation by DEX of the relative proportions of beta 1- and beta 2-AR subtypes in C6 cells. The functional significance of the changing subtype ratios does not appear to be related to catecholamine responsiveness.

Volume 44, Issue 6, pp. 1085-1093, 12/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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