新型KATP开放剂埃他卡林对原代培养人肺动脉平滑肌细胞ERK1/2磷酸化的影响

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (2): 150-154.

新型K_ATP开放剂埃他卡林对原代培养人肺动脉平滑肌细胞ERK1/2磷酸化的影响

梅宏波, 解卫平, 左祥荣, 王虹

南京医科大学附属第一临床医学院呼吸科, 南京210029, 江苏

收稿日期:2008-08-07 修回日期:2008-12-18 出版日期:2009-02-26 发布日期:2020-10-30
通讯作者: 解卫平, 女, 主任医师, 副教授, 硕士研究生导师, 主要从事肺动脉高压的病理学和治疗学研究。Tel:025-83718836-6030 　E-mail:wpxie@njmu.edu.cn
作者简介:梅宏波, 男, 在读硕士研究生, 主要从事肺动脉高压的病理学和治疗学研究。Tel:13675156015 　E-mail:meichongjie1978@yahoo.com.cn
基金资助:
江苏省自然科学基金资助项目(BK2006246)

Effects of iptakalim, a novel ATP-sensitive potassium channel opener, on the phosphorylation of ERK1/2 in primary cultured human pulmonary arterial smooth muscle cells

MEI Hong-bo, XIE Wei-ping, ZUO Xiang-rong, WANG Hong

Respitory Department, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China

Received:2008-08-07 Revised:2008-12-18 Online:2009-02-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:研究新型ATP 敏感性钾通道(KATP)开放剂埃他卡林(IPT) 对内皮素-1(ET-1) 诱导的原代培养人肺动脉平滑肌细胞细胞外信号调节激酶1 和2(ERK1/2) 磷酸化的影响。方法:原代培养人肺动脉平滑肌细胞, 用Western blot 方法检测磷酸化细胞外信号调节激酶1 和2(p-ERK1/2)。培养液中加入ET-1(10 nmol/L), 孵育0 、1 、2 、5 、10 、30 、60 min。培养液中加入ET-1(10 nmol/L) 前30 min 分别加入0.1 、1.0 和10.0 μmol/L IPT, 孵育10 min。培养液中加入ET-1(10 nmol/L) 和IPT(10 μmol/L) 前30 min 加入格列本脲(GLI)(10 μmol/L), 孵育10 min。结果:在2 min 至30 min 之间, ET-1 呈时间依赖性促进人肺动脉平滑肌细胞ERK1/2 磷酸化, 10 min 时最明显。IPT呈浓度依赖性拮抗ET-1 对ERK1/2 磷酸化的影响。特异性KATP 阻断剂GLI 逆转IPT 的作用。结论:IPT 可能通过激活KATP 通道, 抑制ET-1 诱导的原代培养人肺动脉平滑肌细胞ERK1/2 磷酸化, 可能可用于肺血管重构、肺动脉高压的治疗。

关键词: 埃他卡林, ATP 敏感性钾通道, 细胞外信号调节激酶1 和2, 磷酸化细胞外信号调节激酶1和2

Abstract: AIM: To study the effects of iptakalim, a novel ATP-sensitive potassium channel (KATP) opener, on the phosphorylation of extracellular signalregulated kinase1/2 (ERK1/2) induced by endothelin- 1(ET-1) in primary cultured human pulmonary arterial smooth muscle cells.METHODS: By Western blot analysis, the phosphorylation level of ERK1/2 was measured in primary cultured human pulmonary arterial smooth muscle cells.The cells were treated with ET-1 (10 nmol/L) for 0, 1, 2, 5, 10, 30, 60 min, respectively.The cells were pretreated with 0.1, 1.0 and 10 μmol/L iptakalim respectively for 30 min prior to the treatment with ET-1 (10 nmol/L) for 10 min.The cells were pretreated with Glibenclamide(10 μmol/L) for 30 min prior to the treatment with ET-1 (10 nmol/L) and iptakalim (10 μmol/L) for 10 min.RESULTS: ET-1 induced phosphorylation of ERK1/2 from 2 to 30 min with a peak response observed at 10 min in a time-dependent manner.Iptakalim inhibited ET-1-induced ERK1/2 phosphorylation in a concentration-dependent manner.Glibenclamide, a selective KATP channel antagonist, could antagonize the effects of iptakalim. CONCLUSION: Iptakalim inhibited ET-1-induced phosphorylation of ERK1/2 in primary cultured pulmonary arterial smooth muscle cells probably through activating KATP channel and would be a most promising candidate drug to treat the remodeling of pulmonary vasculature and pulmonary arterial hypertension.

Key words: iptakalim, KATP channel, ERK1 2, p-ERK1/2

中图分类号:

R966

梅宏波, 解卫平, 左祥荣, 王虹. 新型K_ATP开放剂埃他卡林对原代培养人肺动脉平滑肌细胞ERK1/2磷酸化的影响[J]. 中国临床药理学与治疗学, 2009, 14(2): 150-154.

MEI Hong-bo, XIE Wei-ping, ZUO Xiang-rong, WANG Hong. Effects of iptakalim, a novel ATP-sensitive potassium channel opener, on the phosphorylation of ERK1/2 in primary cultured human pulmonary arterial smooth muscle cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(2): 150-154.

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