Role of ERK1/2 signaling pathways in 4-aminopyridine-induced rat pulmonary vasoconstriction
- 作者：Weina Han ; Xiaobo Tang ; Hong Wu ; Ye Liu ; Daling Zhu
- 关键词：ERK1/2 ; 4-aminopyridione ; Voltage-gated potassium channels ; Pulmonary artery ; Western blot
- 刊名：European Journal of Pharmacology
- 出版年：2007
- 期刊代码：24_00142999
- 类别：neu
- 出版时间：13 August 2007
- 卷：569
- 期：1-2
- 页码：138-144
- 文件大小：806 K
摘要
The aim of the present study was to investigate the contribution of extracellular signal regulated kinase-1/2 (ERK1/2) to pulmonary artery contraction in response to 4-aminopyridione (4-AP), an inhibitor of a voltage-gated K+ channels that regulate pulmonary vascular tone. Pulmonary artery rings 1–1.5 mm in diameter from male adult Wistar rat were isolated and cut into 3-mm in length. ERK1/2 up-stream kinase (MEK) inhibitors 2′-amino-3′-methoxyflavone (PD98059) and 1,4-diamino-2,3-dicyano-1,4-bis (2-aminophenylthio)-butadiene (U0126), which block the activation of ERK1/2, were used to test the role of ERK1/2 in 4-AP induced pulmonary arterial vasoconstriction and the influences of 4-AP on expressions of phosphorylated ERK1/2 (p-ERK1/2) in cultured rat pulmonary arterial smooth muscle cells (PASMCs) and whole tissues. Our results show that 4-AP elicited concentration-dependent increases in tension of rat pulmonary artery rings, effects that were reduced by pretreatment of the rings with ERK inhibitors, PD98059 (20 μM) and U0126 (10 μM). Moreover, 4-AP increased the expressions of p-ERK1/2 in cultured PASMCs s and whole tissues, which were prevented by pretreatment of the cells or tissues with U0126. These results indicate that ERK1/2 signaling pathway contributes to pulmonary vasoconstriction induced by 4-AP.