Fève B, Baude B, Krief S, Strosberg A D, Pairault J, Emorine L J
U 282 Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Hôpital Henri Mondor, Créteil, France.
J Biol Chem. 1992 Aug 5;267(22):15909-15.
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.
在地塞米松对小鼠3T3-F442A脂肪细胞系β3-肾上腺素能受体（β3AR）表达的调节作用进行了研究。在未处理的细胞中，存在大量对（-）-[3H]CGP12177和（-）-[125I]碘氰吲哚洛尔（对应于β3AR亚型）具有低亲和力的结合位点（62,000 - 114,000个位点/细胞），以及少量对放射性配体具有高亲和力的位点（6,500 - 8,000个位点/细胞）（对应于β1和β2AR亚型的混合物）。细胞长期暴露于250 nM地塞米松导致β3AR密度急剧下降（小于5,000个位点/细胞），这与β3AR选择性激动剂BRL37344和CGP12177刺激细胞内cAMP产生的效力降低相平行。通过聚合酶链反应和核转录分析对RNA进行分析表明，地塞米松抑制β3AR mRNA的合成，导致该mRNA的稳态水平下降4 - 8倍。如抗糖皮质激素RU38486的拮抗作用所评估的，β3AR蛋白和细胞mRNA的下调似乎是由糖皮质激素受体介导的。
