CLOSE RECIPROCAL REGULATION OF BETA(1)-ADRENERGIC AND BETA(2)-ADRENERGIC RECEPTORS BY DEXAMETHASONE IN C6 GLIOMA-CELLS - EFFECTS ON CATECHOLAMINE RESPONSIVENESS

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 [I-125]-cyanopindolol showed that beta1- and beta2-ARs co-existed in this cell line in approximately an 80:20 ratio. Norepinephrine (NE) an d epinephrine (EPI) were equally potent in increasing cAMP accumulatio n, consistent with a primarily beta1-response, although both beta1- an d beta2-components of the response could be isolated using selective a gonists (NE and zinterol), and antagonists (CGP 20712A and ICI 118,551 ). Little or no evidence Of beta3-ARs could be found in this cell line . Treatment of cells with 500 nm dexamethasone (DEX) for 48 hr increas ed the proportion Of beta2-ARs (20 to 60%). However, a reciprocal decr ease in beta1-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 beta2-ARs were closely link ed to decreases in beta1-ARs with little or no change in total recepto r density observed at any time or in any concentration studied. Treatm ent with DEX also increased beta2- and decreased beta1-mediated cAMP r esponses, but did not alter the response to the nonselective agonist, isoproterenol. Northern blot analysis showed a 2- to 3-fold increase i n beta2-AR mRNA, but no change in beta1-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 r esponses to the beta2-selective agonist, zinterol, were increased. The se studies show a close reciprocal regulation by DEX of the relative p roportions of beta1- and beta2-AR subtypes in C6 cells. The functional significance of the changing subtype ratios does not appear to be rel ated to catecholamine responsiveness.