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Dexamethasone regulates beta adrenergic receptors in 3T3-L1 fibroblasts

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5234290
3T3-L1 fibroblasts, containing ..beta..-adrenergic receptors (..beta..AR) of predominantly the ..beta../sub 1/AR subtype, express only ..beta../sub 2/AR after 48 hr treatment with 250 nM dexamethasone (dex). A two-fold increase in ..beta..AR number was also observed upon dex treatment. ..beta..AR were assayed in membranes using the radioligand (/sup 125/I)-cyanopindolol and the ..beta../sub 2/AR selective antagonist ICI. The relative potency of agonists in stimulating whole cell adenylate cyclase activity was consistent with the subtypes determined by binding experiments. The ability of compounds to cause the subtype switch correlates with glucocorticoid activity since these compounds were more effective in facilitating the subtype conversion and the increase in ..beta..AR number than mineralocorticoids. Sex steroids and thyroid hormone were ineffective at concentrations up to 1..mu..M in causing these changes. RNA and protein synthesis appear to be required for the ..beta..AR subtype switch and increase in ..beta..AR number since these changes were not observed with dex treatment in the presence of 1..mu..g/ml actinomycin D or 1..mu..g/ml cyclohexamide. This study suggests that glucocorticoids may induce gene activation in 3T3-L1 fibroblasts that results in an increase in ..beta..AR number and a shift in subtype.
Research Organization:
SmithKline and French Labs., Philadelphia, PA
OSTI ID:
5234290
Report Number(s):
CONF-8606151-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
Country of Publication:
United States
Language:
English

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