Agonist-induced destabilization of beta-adrenergic receptor mRNA. Attenuation of glucocorticoid-induced up-regulation of beta-adrenergic receptors.
Agonist-induced destabilization of beta-adrenergic receptor mRNA. Attenuation of glucocorticoid-induced up-regulation of beta-adrenergic receptors.
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发表时间：
1989
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通讯作者：
J. Hadcock;H. Wang;C. Malbon
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作者：
J. Hadcock;H. Wang;C. Malbon
β-肾上腺素能受体表达和受体mRNA水平被β-肾上腺素能激动剂下调，并被糖皮质激素上调。在DDT 1 MF-2仓鼠输精管细胞中，在受体和受体mRNA水平上研究了这两种相反的调节途径之间的相互作用。地塞米松钝化了单独异丙肾上腺素诱导的受体表达的显着下降，如使用抗受体抗体的间接免疫荧光可见。通过DNA过量溶液杂交定量受体mRNA水平。地塞米松刺激受体mRNA的急剧增加，在4小时后加入类固醇在不存在或存在异丙肾上腺素。到12小时，地塞米松处理导致受体mRNA的新的稳态水平是未处理细胞中观察到的两倍。异丙肾上腺素在12 h时可减弱地塞米松的作用。用异丙肾上腺素和地塞米松组合处理的细胞显示出新的稳态水平，仅比未处理的细胞高30%。通过细胞核连续检测，受体基因的转录速率在单独用异丙肾上腺素激发的细胞中不受影响。相反，地塞米松刺激β 2-肾上腺素能受体基因转录增加4倍。异丙肾上腺素和地塞米松联合促进的转录速率与地塞米松单独相当。受体mRNA在未处理和地塞米松处理的细胞中的半衰期为12 h。与此相反，β-肾上腺素能受体mRNA的半衰期下降到5小时，在地塞米松的存在或不存在下，用异丙肾上腺素处理的细胞。激动剂促进的去稳定化和类固醇诱导的转录提供了两种控制受体mRNA水平的相反途径相互作用的机制。
beta-Adrenergic receptor expression and receptor mRNA levels are down-regulated by beta-adrenergic agonists and up-regulated by glucocorticoids. The interaction between these two opposing regulatory pathways was investigated at the levels of receptor and receptor mRNA in DDT1 MF-2 hamster vas deferens cells. Dexamethasone blunted a marked decrease in receptor expression induced by isoproterenol alone, as made visible by indirect immunofluorescence using antireceptor antibodies. Receptor mRNA levels were quantified by DNA-excess solution hybridization. Dexamethasone stimulated a sharp increase in receptor mRNA at 4 h following the addition of steroid in either the absence or the presence of isoproterenol. By 12 h, dexamethasone treatment resulted in a new steady-state level of receptor mRNA double that observed in untreated cells. Isoproterenol blunted the dexamethasone effect observed at 12 h. Cells treated with isoproterenol and dexamethasone in combination displayed a new steady-state level only 30% greater than untreated cells. Measured by nuclear run-on assays, transcription rates of the receptor gene were unaffected in cells challenged with isoproterenol alone. Dexamethasone, in contrast, stimulated a 4-fold increase in beta 2-adrenergic receptor gene transcription. Isoproterenol and dexamethasone in combination promoted a transcription rate comparable to dexamethasone alone. The half-life of receptor mRNA in untreated and dexamethasone-treated cells was 12 h. In contrast, beta-adrenergic receptor mRNA half-life declined to 5 h in cells that were treated with isoproterenol in the presence or absence of dexamethasone. Agonist-promoted destabilization and steroid-induced transcription provide mechanisms for the interplay of two opposing pathways controlling receptor mRNA levels.