PT - JOURNAL ARTICLE AU - Carr, Michael J. AU - Kollarik, Marian AU - Meeker, Sonya N. AU - Undem, Bradley J. TI - A Role for TRPV1 in Bradykinin-Induced Excitation of Vagal Airway Afferent Nerve Terminals AID - 10.1124/jpet.102.043422 DP - 2003 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1275--1279 VI - 304 IP - 3 4099 - http://jpet.aspetjournals.org/content/304/3/1275.short 4100 - http://jpet.aspetjournals.org/content/304/3/1275.full SO - J Pharmacol Exp Ther2003 Mar 01; 304 AB - 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. The American Society for Pharmacology and Experimental Therapeutics