A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals
A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals
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DOI：
10.1124/jpet.102.043422
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发表时间：
2003-03-01
影响因子：
3.5
通讯作者：
Undem, BJ
中科院分区：
文献类型：
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作者：
Carr, MJ;Kollarik, M;Undem, BJ
利用单细胞外记录技术，我们研究了香草受体-1 （VR1又称TRPV1）在豚鼠离体气道缓激肽诱导的迷走神经传入c纤维接受野激活中的作用。在17条气道c纤维中，14条纤维对缓激素和辣椒素有反应，2条纤维对辣椒素和缓激素均无反应，1条纤维对辣椒素有反应，但对缓激素无反应。因此，每一种缓激肽反应的c -纤维也对辣椒素有反应。缓激素（200 μ l 0.3 μ m溶液）在c -纤维中引起约130个动作电位的爆发。在TRPV1拮抗剂capsazepine （10 muM）存在时，缓激肽引起的动作电位减少83 +/- 9% （n = 6; P < 0.01）。同样，TRPV1阻滞剂钌红（10 μM）对缓激肽诱发动作电位的抑制作用为75 +/- 10% （n = 4; P < 0.05）。在脂氧合酶和环氧合酶抑制剂5,8,11,14-二碳四氰酸（10mum）的存在下，缓激肽诱导的动作电位数量减少了76 +/- 10% （n = 6; P < 0.05）。同样，12-脂氧合酶抑制剂黄芩素（10 μM）与5-脂氧合酶抑制剂ZD2138[6-[3-氟-5[4-甲氧基- 3,4,5,6-四氢- 2h -吡喃-4-基])苯氧基甲基]1-甲基-2-喹诺酮]（10 μM）联合使用可显著抑制缓激肽诱导的反应。我们的数据表明，脂氧合酶产物在缓激肽B-2受体诱导的豚鼠气管内传入c纤维外周末端TRPV1的激活中起作用。
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 mul of 0.3 muM solution) evoked a burst of approximately 130 action potentials in C-fibers. In the presence of the TRPV1 antagonist capsazepine (10 muM), 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 muM), 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 B-2 receptor-induced activation of TRPV1 in the peripheral terminals of afferent C-fibers within guinea pig trachea.