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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals

Michael J. Carr, Marian Kollarik, Sonya N. Meeker and Bradley J. Undem
Journal of Pharmacology and Experimental Therapeutics March 2003, 304 (3) 1275-1279; DOI: https://doi.org/10.1124/jpet.102.043422
Michael J. Carr
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Marian Kollarik
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Sonya N. Meeker
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Bradley J. Undem
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Abstract

Using single-unit extracellular recording techniques, we have examined the role of the vanilloid receptor-1 (VR1 aka TRPV1) in bradykinin-induced activation of vagal afferent C-fiber receptive fields in guinea pig isolated airways. Of 17 airway C-fibers tested, 14 responded to bradykinin and capsaicin, 2 fibers responded to neither capsaicin nor bradykinin, and 1 fiber responded to capsaicin but not bradykinin. Thus, every bradykinin-responsive C-fiber was also responsive to capsaicin. Bradykinin (200 μl of 0.3 μM solution) evoked a burst of approximately 130 action potentials in C-fibers. In the presence of the TRPV1 antagonist capsazepine (10 μM), bradykinin evoked 83 ± 9% (n = 6; P< 0.01) fewer action potentials. Similarly, the TRPV1 blocker, ruthenium red (10 μM), inhibited the number of bradykinin-evoked action potentials by 75 ± 10% (n = 4;P < 0.05). In the presence of 5,8,11,14-eicosatetraynoic acid (10 μM), an inhibitor of lipoxygenase and cyclooxygenase enzymes, the number of bradykinin-induced action potentials was reduced by 76 ± 10% (n = 6; P < 0.05). Similarly, a combination of the 12-lipoxygenase inhibitor, baicalein (10 μM) and the 5-lipoxygenase inhibitor ZD2138 [6-[3-fluoro-5-[4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl])phenoxy-methyl]-1-methyl-2-quinolone] (10 μM) caused significant inhibition of bradykinin-induced responses. Our data suggest a role for lipoxygenase products in bradykinin B2 receptor-induced activation of TRPV1 in the peripheral terminals of afferent C-fibers within guinea pig trachea.

Footnotes

  • This work was supported by grants from the National Institutes of Health.

  • DOI: 10.1124/jpet.102.043422

  • Abbreviations:
    KBS
    Krebs' bicarbonate buffer solution
    ETYA
    5,8,11,14-eicosatetraynoic acid
    AACOCF3
    arachidonyl trifluoromethyl ketone
    ZD2138
    6-[3-fluoro-5-[4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl])phenoxy-methyl]-1-methyl-2-quinolone
    RHC 80267
    1,6-bis(cyclohexyloximinocarbonylamino)hexane
    • Received August 27, 2002.
    • Accepted November 26, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 304 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 304, Issue 3
1 Mar 2003
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals

Michael J. Carr, Marian Kollarik, Sonya N. Meeker and Bradley J. Undem
Journal of Pharmacology and Experimental Therapeutics March 1, 2003, 304 (3) 1275-1279; DOI: https://doi.org/10.1124/jpet.102.043422

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals

Michael J. Carr, Marian Kollarik, Sonya N. Meeker and Bradley J. Undem
Journal of Pharmacology and Experimental Therapeutics March 1, 2003, 304 (3) 1275-1279; DOI: https://doi.org/10.1124/jpet.102.043422
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