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Myosin light‐chain kinase regulates endothelial calcium entry and endothelium‐dependent vasodilation
Author(s) -
Watanabe Hiroshi,
Tran QuangKim,
Takeuchi Kazuhiko,
Fukao Mitsuhiro,
Liu Ming Y.,
Kanno Morio,
Hayashi Toshio,
Iguchi Akihisa,
Seto Minoru,
Ohashi Kyoichi
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0587fje
Subject(s) - myosin light chain kinase , bradykinin , phosphorylation , microbiology and biotechnology , myosin light chain phosphatase , myosin , chemistry , endothelium , protein kinase c , medicine , endocrinology , biology , biochemistry , receptor
ABSTRACT Activation of smooth muscle myosin light‐chain kinase (MLCK) causes contraction. Here we have proven that MLCK controls Ca 2+ entry (CE) in endothelial cells (ECs): MLCK antisense oligonucleotides strongly prevented bradykinin (BK)‐ and thapsigargin (TG)‐induced endothelial Ca 2+ response, while MLCK sense did not. We also show that the relevant mechanism is not phosphorylation of myosin light‐chain (MLC): MLC phosphorylation by BK required CE, but MLC phosphorylation caused by the phosphatase inhibitor calyculin A did not trigger Ca 2+ response. Most important, we provide for the first time strong evidence that, in contrast to its role in smooth muscle cells, activation of MLCK in ECs stimulates the production of important endothelium‐derived vascular relaxing factors: MLCK antisense and MLCK inhibitors abolished BK‐ and TG‐induced nitric oxide production, and MLCK inhibitors substantially inhibited acetylcholine‐stimulated hyperpolarization of smooth muscle cell membrane in rat mesenteric artery. These results indicate that MLCK controls endothelial CE, but not through MLC phosphorylation, and unveils a hitherto unknown physiological function of the enzyme: vasodilation through its action in endothelial cells. The study discovers a counter‐balancing role of MLCK in the regulation of vascular tone.