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

AIM:To study the effects of iptakalim,a novel ATP-sensitive potassium channel(KATP)opener,on the phosphorylation of extracellular signal-regulated 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.