A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals.
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 microl of 0.3 microM solution) evoked a burst of approximately 130 action potentials in C-fibers. In the presence of the TRPV1 antagonist capsazepine (10 microM), bradykinin evoked 83 +/- 9% (n = 6; P < 0.01) fewer action potentials. Similarly, the TRPV1 blocker, ruthenium red (10 microM), 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 microM), 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 microM) 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 microM) caused significant inhibition of bradykinin-induced responses. Our data suggest a role for lipoxygenase products in bradykinin B(2) receptor-induced activation of TRPV1 in the peripheral terminals of afferent C-fibers within guinea pig trachea.
Carr
Michael J
MJ
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA.
Kollarik
Marian
M
Meeker
Sonya N
SN
Undem
Bradley J
BJ
D000818:Animals; D001016:Aortic Bodies / Q000502:physiology*; D001920:Bradykinin / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D008084:Lipoxygenase / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D011955:Receptors, Drug / Q000502:physiology*; D012430:Ruthenium Red / Q000494:pharmacology
D011955:Receptors, Drug; D012430:Ruthenium Red; D008084:Lipoxygenase; D002211:Capsaicin; D001920:Bradykinin