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Journal of Pharmacology and Experimental Therapeutics

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Research ArticleCELLULAR AND MOLECULAR

Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter

E. E. Daniel, T. J. Bowes and J. Jury
Journal of Pharmacology and Experimental Therapeutics June 2002, 301 (3) 1111-1118; DOI: https://doi.org/10.1124/jpet.301.3.1111
E. E. Daniel
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T. J. Bowes
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J. Jury
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Abstract

Whether cGMP and cytosolic guanylate cyclase (cGC) mediate responses of canine lower esophageal sphincter (LES) to nitric oxide (NO) released from nerves, produced in muscle, or added exogenously was evaluated in vitro. 1-H-(1,2,4)oxadiazole(4,3-α)quinoxalin-1-1 (ODQ), inhibitor of cGC, reduced relaxations to nerve stimulation and sodium nitroprusside but not to nitric-oxide synthase activity-dependent outward K+-currents in isolated muscle cells. ODQ also failed to increase tone after nerve blockade. Nonspecific K+ channel blocker, TEA ion at 20 mM was previously shown to increase tone, occlude NO-mediated modulation of tone, and inhibit NO-dependent outward currents but not neural relaxation in LES cells . In this study, TEA abolished neural relaxation and nearly abolished relaxation to sodium nitroprusside when present with ODQ. We conclude that mechanisms coupling NO in canine LES to responses vary with the source of NO. ODQ-dependent mechanisms, presumably involving cGC, mediate actions of NO from nerves, but NO from muscle utilizes TEA-sensitive but not ODQ-dependent mechanisms to modulate tone and outward currents. Exogenous NO utilizes both TEA- and ODQ-dependent mechanisms.

Footnotes

  • ↵1 Current address: Department of Pharmacology, University of Alberta, 9-70 Medical Sciences Building, Edmonton, AB T6G 2H7, Canada.

  • Supported by the Medical Research Council, Canada.

  • Abbreviations:
    LES
    lower esophageal sphincter
    NO
    nitric oxide
    cGC
    cytosolic guanylate cyclase
    EFS
    electrical field stimulation
    ODQ
    1-H-(1,2,4)oxadiazole(4,3-α)quinoxalin-1-1
    l-NAME
    Nω-nitro-l-arginine methyl ester
    ICC
    interstitial cells of Cajal
    pps
    pulses per second
    BKCa channels
    large conductance Ca2+-dependent K+ channels
    l-NOARG
    N-nitro-l-arginine
    ANOVA
    analysis of variance
    • Received October 2, 2001.
    • Accepted February 19, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 301 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 3
1 Jun 2002
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Research ArticleCELLULAR AND MOLECULAR

Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter

E. E. Daniel, T. J. Bowes and J. Jury
Journal of Pharmacology and Experimental Therapeutics June 1, 2002, 301 (3) 1111-1118; DOI: https://doi.org/10.1124/jpet.301.3.1111

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Research ArticleCELLULAR AND MOLECULAR

Roles of Guanylate Cyclase in Responses to Myogenic and Neural Nitric Oxide in Canine Lower Esophageal Sphincter

E. E. Daniel, T. J. Bowes and J. Jury
Journal of Pharmacology and Experimental Therapeutics June 1, 2002, 301 (3) 1111-1118; DOI: https://doi.org/10.1124/jpet.301.3.1111
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