Inhibition by dexamethasone of beta 3-adrenergic receptor responsiveness in 3T3-F442A adipocytes. Evidence for a transcriptional mechanism.
J Biol Chem
; 267(22): 15909-15, 1992 Aug 05.
Article
en En
| MEDLINE
| ID: mdl-1379241
ABSTRACT
Modulation of beta 3-adrenergic receptor (beta 3AR) expression by dexamethasone was investigated in the murine 3T3-F442A adipocytic cell line. In untreated cells, a major population of binding sites (62,000-114,000 sites/cell) of low affinity for (-)-[3H] CGP12177 and (-)-[125I]iodocyanopindolol (corresponding to the beta 3AR subtype) was present along with a minor population (6,500-8,000 sites/cell) of sites of high affinity for the radioligands (corresponding to a mixture of the beta 1 and beta 2AR subtypes). Long-term exposure of the cells to 250 nM dexamethasone led to a sharp decrease in beta 3AR density (less than 5,000 sites/cell) which paralleled a diminished potency of the beta 3AR-selective agonists BRL37344 and CGP12177 to stimulate the production of intracellular cAMP. Analysis of RNA by polymerase chain reaction and nuclear run-on assays indicated that dexamethasone inhibited the synthesis of beta 3AR mRNA, resulting in 4-8-fold decrease in the steady-state levels of this mRNA. The down-regulation of beta 3AR protein and cellular mRNA appeared to be mediated by the receptor for glucocorticoids as assessed by the antagonistic action of the anti-glucocorticoid RU38486.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Dexametasona
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Tejido Adiposo
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Receptores Adrenérgicos beta
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Agonistas Adrenérgicos beta
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Etanolaminas
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Isoproterenol
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
1992
Tipo del documento:
Article
País de afiliación:
Francia