A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals

Michael J. Carr, Marian Kollarik, Sonya Meeker, Bradley J Undem

Research output: Contribution to journalArticle

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 μI 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.

Original languageEnglish (US)
Pages (from-to)1275-1279
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume304
Issue number3
DOIs
StatePublished - Mar 1 2003

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Bradykinin
Unmyelinated Nerve Fibers
Capsaicin
Lipoxygenase Inhibitors
Action Potentials
Guinea Pigs
5,8,11,14-Eicosatetraynoic Acid
Bradykinin B2 Receptors
Pyrans
Ruthenium Red
Lipoxygenase
Cyclooxygenase Inhibitors
Trachea
Evoked Potentials

ASJC Scopus subject areas

  • Pharmacology

Cite this

A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals. / Carr, Michael J.; Kollarik, Marian; Meeker, Sonya; Undem, Bradley J.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 304, No. 3, 01.03.2003, p. 1275-1279.

Research output: Contribution to journalArticle

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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 μI 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.",
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