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

Abstract

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

CLC Number:

R966

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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