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Journal of Cellular Biochemistry

Inhibition of cerebellar nitric oxide synthase and cyclic GMP production by melatonin via complex formation with calmodulin

Authors

  • David Pozo,

    1. Department of Medical Biochemistry and Molecular Biology, The University of Seville School of Medicine and Virgen Macarena Hospital, Seville, Spain
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  • Russel J. Reiter,

    1. Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas
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  • Juan R. Calvo,

    1. Department of Medical Biochemistry and Molecular Biology, The University of Seville School of Medicine and Virgen Macarena Hospital, Seville, Spain
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  • Juan M. Guerrero

    Corresponding author
    1. Department of Medical Biochemistry and Molecular Biology, The University of Seville School of Medicine and Virgen Macarena Hospital, Seville, Spain
    • Department of Medical Biochemistry and Molecular Biology, The University of Seville School of Medicine, Avda Sanchez Pizjuan 4, 41009-Seville, Spain
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Abstract

Constitutive rat cerebellar nitric oxide synthase (NOS) activity is shown to be inhibited by physiological concentrations of the pineal hormone melatonin. The inhibition was dose-dependent and was coupled to an inhibition of the cyclic GMP production activated by L-arginine. Results also show that calmodulin appears to be involved in this process because its presence in the incubation medium was able to prevent the effect of melatonin on both NOS activity and cyclic GMP production. Moreover, polyacrylamide gel electrophoresis studies suggest that melatonin can interact with calmodulin modifying the binding of the peptide to the synthetic NOS peptide encompassing the calmodulin-binding domain of constitutive NOS from rat cerebellum, the natural mechanism by which calmodulin activates cerebellar NOS. J. Cell. Biochem. 65:430–442. © 1997 Wiley-Liss, Inc.

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