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Rho‐kinase inhibitor inhibits both myosin phosphorylation‐dependent and ‐independent enhancement of myofilament Ca 2+ sensitivity in the bovine middle cerebral artery
Author(s) -
Maeda Yoshihisa,
Hirano Katsuya,
Nishimura Junji,
Sasaki Tomio,
Kanaide Hideo
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705487
Subject(s) - wortmannin , myosin light chain kinase , phosphorylation , rho associated protein kinase , protein kinase c , rho kinase inhibitor , contraction (grammar) , kinase , myosin , muscle contraction , chemistry , biophysics , medicine , endocrinology , microbiology and biotechnology , biology , biochemistry , phosphatidylinositol
The role of Rho kinase in Ca 2+ sensitization of the contractile apparatus in smooth muscle was investigated in the bovine middle cerebral artery. U46619, a thromboxane A 2 analog, induced a greater sustained contraction with a smaller [Ca 2+ ] i elevation than that seen with 118 m M K + . The level of myosin light chain (MLC) phosphorylation obtained in the initial phase of the contraction was higher than that seen with 118 m M K + ; thereafter, it gradually declined to a comparable level in the late phase. During the steady state of the U46619‐induced contraction, Y27632 (10 μ M ), a Rho‐kinase inhibitor, partially inhibited [Ca 2+ ] i , although it substantially inhibited tension and MLC phosphorylation. Wortmannin (10 μ M ), an MLC kinase inhibitor, had no significant effect on [Ca 2+ ] i , but it completely inhibited MLC phosphorylation and partially inhibited tension. The wortmannin‐resistant tension development was thus not associated with MLC phosphorylation, and this component was completely inhibited by Y27632. In conclusion, U46619 enhanced Ca 2+ sensitivity in a manner both dependent and independent of MLC phosphorylation in the bovine middle cerebral artery. Both mechanisms of Ca 2+ sensitization can be inhibited by the Rho‐kinase inhibitor.British Journal of Pharmacology (2003) 140 , 871–880. doi: 10.1038/sj.bjp.0705487