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Cyclic Nucleotide-Gated Channels Contribute to Thromboxane A(2)-Induced Contraction of Rat Small Mesenteric Arteries

BACKGROUND: Thromboxane A(2) (TxA(2))-induced smooth muscle contraction has been implicated in cardiovascular, renal and respiratory diseases. This contraction can be partly attributed to TxA(2)-induced Ca(2+) influx, which resulted in vascular contraction via Ca(2+)-calmodulin-MLCK pathway. This st...

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Detalles Bibliográficos
Autores principales: Leung, Yuk Ki, Du, Juan, Huang, Yu, Yao, Xiaoqiang
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885410/
https://www.ncbi.nlm.nih.gov/pubmed/20559420
http://dx.doi.org/10.1371/journal.pone.0011098
Descripción
Sumario:BACKGROUND: Thromboxane A(2) (TxA(2))-induced smooth muscle contraction has been implicated in cardiovascular, renal and respiratory diseases. This contraction can be partly attributed to TxA(2)-induced Ca(2+) influx, which resulted in vascular contraction via Ca(2+)-calmodulin-MLCK pathway. This study aims to identify the channels that mediate TxA(2)-induced Ca(2+) influx in vascular smooth muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Application of U-46619, a thromboxane A(2) mimic, resulted in a constriction in endothelium-denuded small mesenteric artery segments. The constriction relies on the presence of extracellular Ca(2+), because removal of extracellular Ca(2+) abolished the constriction. This constriction was partially inhibited by an L-type Ca(2+) channel inhibitor nifedipine (0.5–1 µM). The remaining component was inhibited by L-cis-diltiazem, a selective inhibitor for CNG channels, in a dose-dependent manner. Another CNG channel blocker LY83583 [6-(phenylamino)-5,8-quinolinedione] had similar effect. In the primary cultured smooth muscle cells derived from rat aorta, application of U46619 (100 nM) induced a rise in cytosolic Ca(2+) ([Ca(2+)](i)), which was inhibited by L-cis-diltiazem. Immunoblot experiments confirmed the presence of CNGA2 protein in vascular smooth muscle cells. CONCLUSIONS/SIGNIFICANCE: These data suggest a functional role of CNG channels in U-46619-induced Ca(2+) influx and contraction of smooth muscle cells.