埃他卡林对大鼠尾动脉平滑肌细胞[Ca^(2+)]_i,PKA和PKC活性的影响  

Effects of iptakalim on intracellular calcium concentrations, PKA and PKC activities in rat tail artery smooth muscle cells

作　　者：高敏[1] 王玉[1] 汪海[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《药学学报》2005年第10期954-957,共4页Acta Pharmaceutica Sinica

基　　金：国家高技术研究发展计划(863计划)重大专项资助项目(2002AA2Z3137).

摘　　要：Aim To investigate the effects of iptakalim, a new structural potassium channel opener （KCO）, on intracellular calcium concentration ([Ca2+]i), protein kinase C （PKC）, and cAMP-dependent kinase （PKA） activities in rat tail artery smooth muscle cells （RTA-SMC）, and to analyze mechanisms involved in iptakalim reversing hypertensive vascular remodeling. Methods RTA-SMC was cultured and passages 3-4 were used for experiment. [Ca2+]i was measured by laser scanning confocal microscope after loaded with fluorescent indicator fluo-3-acetoxymethylester, and activities of PKA and PKC were detected by commercial assay kits （the nonradioactive PepTag system） following instructions. Results Compared with baseline, [Ca2+]i reduced significantly after iptakalim- or pinacidil-treatment at concentrations of 0.1, 1 and 10 (μmol·L-1), while diazoxide caused significant decrease at concentration of 1 and 10 (μmol·L-1). After preincubation with 1 (μmol·L-1) glibenclamide, [Ca2+]i was not significantly changed when iptakalim, pinacidil or diazoxide were added at concentration of 0.1 and 1 (μmol·L-1). Activities of PKA and PKC increased significantly by 1 μmol·L-1 iptakalim- or pinacidil-treatment, while 1 μmol·L-1 diazoxide induced significant change in activity of PKC but not in that of PKA. Conclusion The characteristics of iptakalim on [Ca2+]i, PKA and PKC are more or less similar to those of pinacidil. Iptakalim decreased [Ca2+]i while increased PKA and PKC activities of RTA-SMCs, which may contribute to its ability to reverse antihypertensive vascular remodeling.Aim To investigate the effects of iptakalim, a new structural potassium channel opener （KCO）, on intracellular calcium concentration （[Ca^2＋]i）, protein kinase C （PKC）, and cAMP- dependent kinase （PKA） activities in rat tail artery smooth muscle cells （RTA-SMC）, and to analyze mechanisms involved in iptakalim reversing hypertensive vascular remodeling. Methods RTA-SMC was cultured and passages 3-4 were used for experiment. [ Ca^2＋ ]i was measured by laser scanning confocal microscope after loaded with fluorescent indicator fluo-3-acetoxymethylester, and activities of PKA and PKC were detected by commercial assay kits （the nonradioactive PepTag system） following instructions. Results Compared with baseline, [ Ca^2＋ ]i reduced significantly after iptakalim- or pinacidil-treatment at concentrations of 0. 1, 1 and 10 μmol · L^-1, while diazoxide caused significant decrease at concentration of 1 and 10 μmol · L^-1. After preincubation with 1 μmol · L^-1 glibenclamide, [ Ca^2＋ ]i was not significantly changed when iptakalim, pinacidil or diazoxide were added at concentration of 0. 1 and 1 μmol · L^-1. Activities of PKA and PKC increased significantly by 1 μmol · L^-1iptakalim- or pinacidil- treatment, while 1 μmol · L^- diazoxide induced significant change in activity of PKC but not in that of PKA. Conclusion The characteristics of iptakalim on [ Ca^2＋ ]i, PKA and PKC are more or less similar to those of pinacidil. Iptakalim decreased [ Ca^2 ＋ ] i while increased PKA and PKC activities of RTA-SMCs, which may contribute to its ability to reverse antihypertensive vascular remodeling.

关 键 词：埃他卡林 细胞内钙浓度 cAMP依赖性蛋白激酶 蛋白激酶C 大鼠尾动脉平滑肌细胞 

分 类 号：R963[医药卫生—微生物与生化药学] R329.251[医药卫生—药理学]