Effect Of Iptakalim, A Novel Atp-sensitivepotassium Channel Opener, On The Phosphory Of Erk1/2 In Primary Cultured Human Pulmonary Arterial Smooth Muscle Cells

Objective: To study the effects of iptakalim,a novel adenosine-triphosphate(ATP)-sensitive potassium channel(KATP)opener,on the phosphorylation of extracellularsignal-regulated kinase1/2(ERK1/2)induced by endothelin-1(ET-1)in primarycultured human pulmonary arterial smooth muscle cells.Methods: By Western-blot analysis, the phosphorylation level of ERK1/2 wasmeasured in primary cultured human pulmonary arterial smooth muscle cells.①Thecells were treated with ET-1 (10 nmol/L) for 0, 1, 2, 5, 10, 30, 60 min, respectively.②The cells were pretreated with iptakalim 10μmol/L for 30 min prior to the treatmentwith ET-1 for 0, 1, 2, 5, 10, 30, 60 min, respectively.③The cells were pretreatedwith 0.1, 1.0 and 10μmol/L iptakalim respectively for 30 min prior to the treatmentwith ET-1 (10 nmol/L) for 10 min.④The cells were pretreated with glibenclamide(10μmol/L) for 30 min prior to the treatment with ET-1 (10 nmol/L) and iptakalim (10μmol/L) for 10 min.Results:①ET-1 induced phosphorylation of ERK1/2 from 2 to 30 min with a peakresponse observed at 10 min in a time-dependent manner.②Iptakalim inhibited ET-1-induced ERK1/2 phosphorylation in a time-independent manner.③Iptakaliminhibited ET-1-induced ERK1/2 phosphorylation in a concentration-dependent manner.④Glibenclamide, a selective KATP channel antagonist, could antagonize theeffects of iptakalim.ConclusiConclusion: Iptakalim inhibited ET-1-induced phosphorylation of ERK1/2 in primarycultured pulmonary arterial smooth muscle cells probably through activating KATPchannels and will be a most promising candidate drug to inhibit the remodeling ofpulmonary vasculature and pulmonary arterial hypertension.