Nishikawa M, Mak J C, Shirasaki H, Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Eur J Pharmacol. 1993 Oct 15;247(2):131-8. doi: 10.1016/0922-4106(93)90070-p.
The down-regulation by isoprenaline of beta 1 and beta 2-adrenoceptors in rat lung was investigated at the receptor protein and messenger RNA level. Rats were treated with either isoprenaline or vehicle for 2 h, 1 day and 7 days. Isoprenaline treatment resulted in significant decreases of both beta 1- and beta 2-adrenoceptor density after 1 day with maximal decreases of 65 +/- 7 and 65 +/- 5% for beta 1- and beta 2-adrenoceptors, respectively, at 7 days. The administration of isoprenaline had no effect on binding affinities of either beta 1 or beta 2-adrenoceptors. beta 1-Adrenoceptor mRNA was significantly decreased by 58 +/- 10, 73 +/- 4 and 51 +/- 11% at 2 h, 1 day and 7 days, respectively, after isoprenaline treatment. However, the beta 2-adrenoceptor mRNA was not changed at 2 h after treatment and was significantly decreased by 35 +/- 11 and 45 +/- 12% at 1 day and 7 days, respectively after treatment. This time course of beta 2-adrenoceptor mRNA correlated well with that of the transcription factor cyclic AMP response element binding protein-like DNA binding activity, determined by gel shift assay. These findings indicate the existence of distinct mechanisms for down-regulation of beta 1- and beta 2-adrenoceptors and suggest the involvement of cyclic AMP response element binding protein in the down-regulation of beta 2-adrenoceptors in rat lung.
在受体蛋白和信使核糖核酸水平上，研究了异丙肾上腺素对大鼠肺中β1和β2肾上腺素能受体的下调作用。大鼠分别用异丙肾上腺素或赋形剂处理2小时、1天和7天。异丙肾上腺素处理1天后，β1和β2肾上腺素能受体密度均显著降低，7天时β1和β2肾上腺素能受体密度最大分别降低65±7%和65±5%。给予异丙肾上腺素对β1或β2肾上腺素能受体的结合亲和力均无影响。异丙肾上腺素处理后2小时、1天和7天，β1肾上腺素能受体信使核糖核酸分别显著降低58±10%、73±4%和51±11%。然而，β2肾上腺素能受体信使核糖核酸在处理后2小时未发生变化，处理后1天和7天分别显著降低35±11%和45±12%。通过凝胶迁移试验测定，β2肾上腺素能受体信使核糖核酸的这一变化过程与转录因子环磷酸腺苷反应元件结合蛋白样DNA结合活性的变化过程密切相关。这些发现表明，β1和β2肾上腺素能受体下调存在不同机制，并提示环磷酸腺苷反应元件结合蛋白参与大鼠肺中β2肾上腺素能受体的下调。
