Abstract
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 microM) and U0126 (10 microM). 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Aminopyridine / pharmacology*
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Animals
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Blotting, Western
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Butadienes / pharmacology
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Cells, Cultured
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Flavonoids / pharmacology
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In Vitro Techniques
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Lung / blood supply
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Lung / drug effects
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Lung / physiology
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MAP Kinase Signaling System / drug effects*
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Male
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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Nitriles / pharmacology
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Phosphorylation / drug effects
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Potassium Channel Blockers / pharmacology
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Potassium Channels, Voltage-Gated / antagonists & inhibitors
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Potassium Channels, Voltage-Gated / physiology
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Pulmonary Artery / cytology
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Pulmonary Artery / drug effects*
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Pulmonary Artery / physiology
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Rats
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Rats, Wistar
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Time Factors
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Vasoconstriction / drug effects*
Substances
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Butadienes
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Enzyme Inhibitors
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Flavonoids
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Nitriles
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Potassium Channel Blockers
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Potassium Channels, Voltage-Gated
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U 0126
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4-Aminopyridine
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Extracellular Signal-Regulated MAP Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one