SELECTIVE DESENSITIZATION OF BETA(1)-ADRENERGIC AND BETA(2)-ADRENERGIC RECEPTORS IN C-6 GLIOMA-CELLS - EFFECTS ON CATECHOLARNINE RESPONSIVENESS

We studied the effects of changing beta(1)- and beta(2)-adrenergic rec eptor (AR) subtype ratios and densities on cyclic AMP (cAMP) responses to norepinephrine (NE) and epinephrine (EPI) in rat C-6 glioma cells. Dexamethasone (DEX) increased beta(2)- and decreased beta(1)-AR expre ssion without changing total beta-AR density, whereas pretreatment wit h selective agonists specifically downregulated each subtype. Combinat ions of these treatments produced cells with six different beta(2)/bet a(1) ratios that ranged from 0 (100% beta(1)) to 2.85. We compared the effects of NE and EPI on cAMP accumulation in each condition and obse rved a predominantly beta(1) pharmacology (NE > EPI) under most condit ions. However, as the beta(2)-AR density exceeded the number of beta(1 )-ARs we observed a progressive shift toward a more beta(2)-like pharm acology (EPI > NE), without the appearance of biphasic concentration-r esponse curves. The ratio of beta(2)/beta(1) density correlated signif icantly (p < 0.006) with the ratio 2 of the potencies of NE and EPI in increasing cAMP formation. We conclude that in native C-6 cells beta( 1)-ARs appear to couple more efficiently to cAMP accumulation than do beta(2)-ARs, but both subtypes contribute to catecholamine responses i n a nonadditive manner when the proportion of beta(2)-ARs is increased .