Independent and coordinate regulation of beta 1- and beta 2-adrenergic receptors in rat C6 glioma cells.
Rat C6 glioma cells have both beta 1- and beta 2-adrenergic receptors in approximately 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 [3H] 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 approximately 90% of the total receptor population by 6 h as measured by the loss of binding of the more hydrophobic ligand [125I]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.
Fishman
P H
PH
Membrane Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Miller
T
T
Curran
P K
PK
Feussner
G K
GK
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D007545:Isoproterenol