Luo Guogang, Jamali Roya, Cao Yong-Xiao, Edvinsson Lars, Xu Cang-Bao
Neurology Department of the First Hospital, Medical College of Xian Jiaotong University, P. R. China.
Eur J Pharmacol. 2006 May 24;538(1-3):124-31. doi: 10.1016/j.ejphar.2006.03.057. Epub 2006 Apr 4.
In cardiovascular diseases, endothelin type B (ET(B)) receptors in arterial smooth muscle cells are upregulated. The present study revealed that organ culture of rat mesenteric artery segments enhanced endothelin ET(B) receptor-mediated contraction paralleled with increase in the receptor mRNA and protein expressions. The endothelin ET(B) receptor-mediated contraction was associated with increase in phosphorylation of extracellular regulation kinase 1 and 2 (ERK1/2) proteins and elevated levels of intracellular calcium. The elevation curve of intracellular calcium consisted of two phases: one rapid and one sustained. Inhibition of ERK1/2 phosphorylation by SB386023 or blockage of calcium channels by nifedipine significantly reduced the endothelin ET(B) receptor-mediated contraction (P<0.05) and decreased the sustained phase of intracellular calcium level, but not the rapid phase. Thus, phosphorylation of ERK1/2 proteins and elevation of intracellular calcium level are required for endothelin ET(B) receptor-mediated contraction in rat mesenteric artery.
在心血管疾病中，动脉平滑肌细胞中的内皮素B（ET(B)）受体上调。本研究表明，大鼠肠系膜动脉段的器官培养增强了内皮素ET(B)受体介导的收缩，同时受体mRNA和蛋白表达增加。内皮素ET(B)受体介导的收缩与细胞外调节激酶1和2（ERK1/2）蛋白磷酸化增加以及细胞内钙水平升高有关。细胞内钙的升高曲线包括两个阶段：一个快速阶段和一个持续阶段。用SB386023抑制ERK1/2磷酸化或用硝苯地平阻断钙通道可显著降低内皮素ET(B)受体介导的收缩（P<0.05），并降低细胞内钙水平的持续阶段，但不影响快速阶段。因此，ERK1/2蛋白的磷酸化和细胞内钙水平的升高是大鼠肠系膜动脉中内皮素ET(B)受体介导收缩所必需的。
