INDEPENDENT AND COORDINATE REGULATION OF BETA(1)-ADRENERGIC AND BETA(2)-ADRENERGIC RECEPTORS IN RAT C6 GLIOMA-CELLS

Rat C6 glioma cells have both beta(1)- and beta(2)-adrenergic receptors in similar to 7:3 ratio. When the cells were exposed to the beta-adrenergic agonist isoproterenol, there was a rapid sequestration of up to 50% of the surface receptor population over a 30-min period as measured by the loss of binding of the hydrophilic ligand [H-3]CGP-12177 to intact cells. Using the beta(1)-selective antagonist CGP 20712A to quantify the proportion of the two subtypes, it was found that although both beta(1) and beta(2) receptors were sequestered, the latter were sequestered initially twice as fast as the former. More prolonged agonist exposure led to a down-regulation of similar to 90% of the total receptor population by 6 h as measured by the loss of binding of the more hydrophobic ligand [I-125] iodocyanopindolol to cell lysates. The two subtypes, however, underwent down-regulation with similar kinetics. Treatment of the cells with agents that raise cyclic AMP levels such as cholera toxin and forskolin resulted in a slower, but still coordinated down-regulation of both subtypes. Thus, there appears to be both independent and coordinate regulation of endogenous beta(1)-and beta(2)-adrenergic receptors in the same cell line.