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  

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

作　　者：梅宏波[1] 解卫平[1] 左祥荣[1] 王虹[1] 

机构地区：[1]南京医科大学附属第一临床医学院呼吸科

出　　处：《中国临床药理学与治疗学》2009年第2期150-154,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：江苏省自然科学基金资助项目(BK2006246)

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(10nmol/L),孵育0、1、2、5、10、30、60min。培养液中加入ET-1(10nmol/L)前30min分别加入0.1、1.0和10.0μmol/LIPT,孵育10min。培养液中加入ET-1(10nmol/L)和IPT(10μmol/L)前30min加入格列本脲(GLI)(10μmol/L),孵育10min。结果:在2min至30min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,10min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。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 puhnonary 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 ceils were pretreated with 0.1, 1.0 and 10 umol/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 umol/L） for 30 min prior to the treatment with ET-1 （ 10 nmol/L） and iptakalim （10 umol/L） for 10 min. RESULTS： ET-1 induced phosphorylation of ERK1/2 from 2 to 30 rain 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. Glibenelamide, a selective KATP channel antagonist, could antagonize the effects of iptakalim. CONCLUSION： Iptakalim inhibited ET-1-indueed phosphorylation of ERK1/2 in primary cuhured 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.

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 

分 类 号：R966[医药卫生—药理学]