Kollarik M, Undem B J
Johns Hopkins Asthma Center, Johns Hopkins School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
J Physiol. 2004 Feb 15;555(Pt 1):115-23. doi: 10.1113/jphysiol.2003.054890. Epub 2003 Nov 21.
The vanilloid receptor TRPV1 (formerly VR1) has been implicated in the activation of nociceptive sensory nerves by capsaicin, noxious heat, protons, bradykinin, cannabinoids such as anandamide, and certain metabolites of arachidonic acid. Using TRPV1 knockout mouse (TRPV1-/-) we address the question of whether TRPV1 is obligatory for action potential discharge in vagal C-fibre terminals evoked by capsaicin, anandamide, acid and bradykinin. The response of a defined subtype of the vagal afferent bronchopulmonary C-fibres (conduction velocity < 0.7 ms(-1)) to the putative TRPV1 activators was studied in vitro in the mouse isolated/perfused lung-nerve preparation. Capsaicin (1 microm) evoked action potential discharge of approximately 90% (28/31) of C-fibres in the TRPV1+/+ mice, but failed to activate bronchopulmonary C-fibres in TRPV1-/- animals (n = 10). Anandamide (3-100 microm) induced concentration-dependent activation of capsaicin-sensitive TRPV1+/+ C-fibres with a threshold of 3-10 microm, but failed to evoke substantive discharge in TRPV1-/- C-fibres. In the TRPV1+/+ mice, the B2 receptor-mediated activation by bradykinin (1 microm) was restricted to the capsaicin-sensitive C-fibres. Bradykinin was effective in evoking B2 receptor-mediated action potential discharge in TRPV1-/- C-fibres, but the response was significantly (P < 0.05) less persistent than in TRPV1+/+ C-fibres. Exposing the tissue to acid (pH = 5) excited both TRPV1+/+ and TRPV1-/- C-fibres. We conclude that TRPV1 is obligatory for vagal C-fibre activation by capsaicin and anandamide. By contrast, whereas TRPV1 may have a modulatory role in bradykinin and acid-induced activation of bronchopulmonary C-fibres, it is not required for action potential discharge evoked by these stimuli.
香草酸受体TRPV1（以前称为VR1）与辣椒素、有害热、质子、缓激肽、大麻素（如花生四烯酸乙醇胺）以及花生四烯酸的某些代谢产物激活伤害性感觉神经有关。我们使用TRPV1基因敲除小鼠（TRPV1-/-）来研究TRPV1对于辣椒素、花生四烯酸乙醇胺、酸和缓激肽诱发的迷走神经C纤维终末动作电位发放是否必不可少。在小鼠离体/灌注肺-神经标本中，体外研究了迷走传入支气管肺C纤维（传导速度<0.7 m/s）的特定亚型对假定的TRPV1激活剂的反应。辣椒素（1 μmol）可诱发TRPV1+/+小鼠中约90%（28/31）的C纤维产生动作电位发放，但未能激活TRPV1-/-动物的支气管肺C纤维（n = 10）。花生四烯酸乙醇胺（3 - 100 μmol）以浓度依赖性方式激活辣椒素敏感的TRPV1+/+ C纤维，阈值为3 - 10 μmol，但未能在TRPV1-/- C纤维中诱发大量发放。在TRPV1+/+小鼠中，缓激肽（1 μmol）介导的B2受体激活仅限于辣椒素敏感的C纤维。缓激肽可有效诱发TRPV1-/- C纤维中B2受体介导的动作电位发放，但该反应的持续性明显（P < 0.05）低于TRPV1+/+ C纤维。将组织暴露于酸性环境（pH = 5）会使TRPV1+/+和TRPV1-/- C纤维都兴奋。我们得出结论，TRPV1对于辣椒素和花生四烯酸乙醇胺激活迷走神经C纤维是必不可少的。相比之下，虽然TRPV1可能在缓激肽和酸诱导的支气管肺C纤维激活中具有调节作用，但这些刺激诱发的动作电位发放并不需要TRPV1。
