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Research ArticleNEUROPHARMACOLOGY

Nitric Oxide Is Involved in Acetylcholinesterase Inhibitor-Induced Myopathy in Rats

Gayathri Jeyarasasingam, Michael Yeluashvili and Maryka Quik
Journal of Pharmacology and Experimental Therapeutics October 2000, 295 (1) 314-320;
Gayathri Jeyarasasingam
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Michael Yeluashvili
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Maryka Quik
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Abstract

Excess activation of muscle nicotinic acetylcholine receptors due to genetic mutations, as seen in slow channel congenital myasthenic syndrome, or acetylcholinesterase (AChE) inhibition results in muscle cell degeneration. Our recent work showed that nitric oxide synthase (NOS) inhibitors prevent nicotine-induced muscle cell death in culture. In the present study, we examined the effects of NOS inhibition on nicotinic receptor-mediated myopathy in vivo. Rats injected with the AChE inhibitor paraoxon demonstrate a 90-fold increase in the number of dying muscle cells compared with control as evidenced histologically by centralized nuclei and the presence of degenerating profiles. Coadministration of the nonspecific NOS inhibitor nitro-l-arginine methyl ester or the neuronal NOS-specific inhibitor 7-nitroindazole dramatically reduced the presence of such degenerating profiles to ∼20% of that seen with paraoxon alone. These results show that inhibition of NOS, as well as neuronal NOS, significantly reduces AChE inhibitor-induced muscle cell degeneration, suggesting that increased nitric oxide production mediates such myopathy.

Footnotes

  • Send reprint requests to: Dr. Maryka Quik, The Parkinson's Institute, 1170 Morse Ave., Sunnyvale, CA 94089-1605. E-mail:mquik{at}parkinsonsinstitute.org

  • ↵1 This study was supported by the Muscular Dystrophy Association, USA #2421, and the California Tobacco Related Disease Program #7FT-0010.

  • ↵2 Present address: Extramural Review Branch, National Institute of Mental Health, 6001 Executive Blvd., Room 6154, MSC 9609, Bethesda, MD 20892-9609 [Rockville, MD 20852 (for express/courier service)].

  • Abbreviations:
    AChE
    acetylcholinesterase
    NO
    nitric oxide
    CNS
    central nervous system
    NMDA
    N-methyl-d-aspartate
    NOS
    nitric oxide synthase
    eNOS
    endothelial nitric oxide synthase
    nNOS
    neuronal nitric oxide synthase
    l-NAME
    nitro-l-arginine methyl ester
    7-NI
    7-nitroindazole
    • Received April 6, 2000.
    • Accepted June 9, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 295 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 295, Issue 1
1 Oct 2000
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Research ArticleNEUROPHARMACOLOGY

Nitric Oxide Is Involved in Acetylcholinesterase Inhibitor-Induced Myopathy in Rats

Gayathri Jeyarasasingam, Michael Yeluashvili and Maryka Quik
Journal of Pharmacology and Experimental Therapeutics October 1, 2000, 295 (1) 314-320;

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Research ArticleNEUROPHARMACOLOGY

Nitric Oxide Is Involved in Acetylcholinesterase Inhibitor-Induced Myopathy in Rats

Gayathri Jeyarasasingam, Michael Yeluashvili and Maryka Quik
Journal of Pharmacology and Experimental Therapeutics October 1, 2000, 295 (1) 314-320;
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