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