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Pharmacomechanical Coupling Through Regulation of Myosin Light Chain Phosphatase

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Regulation of the Contractile Cycle in Smooth Muscle

Summary

The two major components of pharmacomechanical coupling, inositol 1,4,5-trisphosphate-induced Ca2+ release and modulation of Ca2+ sensitivity, are described. Desensitization of phasic smooth muscles to Ca2+ is demonstrated through time-dependent divergence, during relaxation, between the level of Ca2+ and the decline in MLC20 phosphorylation and force. Possible mechanisms of desensitization include down-regulation of myosin light chain kinase and up-regulation of myosin light chain phosphatase. Sensitization to Caz’ is shown to be mediated by a G protein-coupled system that inhibits the (type 1) protein phosphatase responsible for dephosphorylation of the regulatory smooth muscle myosin light chain (MLC20). The diacylglycerol/kinase C system and arachidonic acid are identified as potential messengers mediating the inhibition of MLC20 phosphatase. The inhibitory effects of arachidonic acid on myosin light chain phosphatase, through dissociation of the catalytic from the targeting subunits, are illustrated, and studies showing the inhibition of voltage-gated Ca“ current by arachidonic acid are summarized. It is suggested that G protein-coupled protein phosphatase inhibition plays a significant role in the regulation of nonmuscle functions in which phosphorylation and dephosphorylation of nonmuscle myosins have functionally important effects.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biological Physics, University of Virginia, Health Sciences Center, Box 449, Jordan Hall, Charlottesville, VA, 22908, USA

    A. P. Somlyo, M. Gong, K. Iizuka, T. Haystead & A. V. Somlyo

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  1. A. P. Somlyo
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  2. M. Gong
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  3. K. Iizuka
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  4. T. Haystead
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  5. A. V. Somlyo
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Editors and Affiliations

  1. Mie University of School Medicine, 2-175 Edobashi, Tsu, Mie, 514, Japan

    Takeshi Nakano M.D., Ph.D. (Professor) (Professor)

  2. University of Arizona, 85721, Tucson, AZ, USA

    David J. Hartshorne Ph.D. (Professor) (Professor)

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© 1995 Springer-Verlag Tokyo

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Somlyo, A.P., Gong, M., Iizuka, K., Haystead, T., Somlyo, A.V. (1995). Pharmacomechanical Coupling Through Regulation of Myosin Light Chain Phosphatase. In: Nakano, T., Hartshorne, D.J. (eds) Regulation of the Contractile Cycle in Smooth Muscle. Springer, Tokyo. https://doi.org/10.1007/978-4-431-65880-1_11

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  • DOI: https://doi.org/10.1007/978-4-431-65880-1_11

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-65882-5

  • Online ISBN: 978-4-431-65880-1

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