Okazaki M, Hu Z W, Fujinaga M, Hoffman B B
Department of Medicine, Stanford University School of Medicine, California.
J Clin Invest. 1994 Jul;94(1):210-8. doi: 10.1172/JCI117309.
While growth of blood vessels is important in hypertension, relatively little is known about the contribution of catecholamines. Using isolated rat aorta and cultured smooth muscle cells, we examined adrenergic stimulation of gene expression. Phenylephrine, a selective alpha 1 adrenergic receptor agonist, caused a rapid and transient increase in c-fos mRNA accumulation which was inhibited by prazosin, an alpha 1 receptor antagonist. Similarly, phenylephrine stimulated c-jun and c-myc mRNA accumulation. Chloroethyl-clonidine, a compound which irreversibly blocks alpha 1B receptors, completely blocked the phenylephrine-induced increase in c-fos mRNA. RNase protection experiments demonstrated that rat aorta prominently expressed mRNA for alpha 1B and alpha 1A/D receptors. Phenylephrine-induced c-fos mRNA was partially inhibited by H-7, a protein kinase C inhibitor, and by nifedipine, a Ca2+ channel blocker; these two compounds together had additive effects. In situ hybridization showed that expression of c-fos mRNA induced by phenylephrine was localized to aorta's medial layer. These results suggest that alpha 1 receptor-induced increase in c-fos mRNA in aorta is mediated by a chloroethyl-clonidine-sensitive receptor subtype signaling via increasing intracellular Ca2+ concentrations and activating protein kinase C.
虽然血管生长在高血压中很重要，但关于儿茶酚胺的作用却知之甚少。我们使用离体大鼠主动脉和培养的平滑肌细胞，研究了肾上腺素能刺激对基因表达的影响。苯肾上腺素是一种选择性α1肾上腺素能受体激动剂，可导致c-fos mRNA积累迅速短暂增加，而α1受体拮抗剂哌唑嗪可抑制这种增加。同样，苯肾上腺素刺激了c-jun和c-myc mRNA的积累。氯乙可乐定是一种不可逆地阻断α1B受体的化合物，它完全阻断了苯肾上腺素诱导的c-fos mRNA增加。核糖核酸酶保护实验表明，大鼠主动脉显著表达α1B和α1A/D受体的mRNA。苯肾上腺素诱导的c-fos mRNA受到蛋白激酶C抑制剂H-7和钙通道阻滞剂硝苯地平的部分抑制；这两种化合物共同作用具有相加效应。原位杂交显示，苯肾上腺素诱导的c-fos mRNA表达定位于主动脉中层。这些结果表明，α1受体诱导的主动脉中c-fos mRNA增加是由氯乙可乐定敏感的受体亚型介导的，该亚型通过增加细胞内钙浓度和激活蛋白激酶C来发挥信号传导作用。
