Cellular Mechanism Underlying Formaldehyde-Stimulated Cl− Secretion in Rat Airway Epithelium

BackgroundRecent studies suggest that formaldehyde (FA) could be synthesized endogeneously and transient receptor potential (TRP) channel might be the sensor of FA. However, the physiological significance is still unclear. Methodology/Principal FindingsThe present study investigated the FA induced epithelial Cl- secretion by activation of TRPV-1 channel located in the nerve ending fiber. Exogenously applied FA induced an increase of ISC in intact rat trachea tissue but not in the primary cultured epithelial cells. Western blot and immunofluorescence analysis identified TRPV-1 expression in rat tracheal nerve ending. Capsazepine (CAZ), a TRPV-1 specific antagonist significantly blocked the ISC induced by FA. The TRPV-1 agonist capsaicin (Cap) induced an increase of ISC, which was similar to the ISC induced by FA. L-703606, an NK-1 specific inhibitor and propranolol, an adrenalin β receptor inhibitor significantly abolished the ISC induced by FA or Cap. In the ion substitute analysis, FA could not induce ISC in the absence of extracelluar Cl-. The ISC induced by FA could be blocked by the non-specific Cl- channel inhibitor DPC and the CFTR specific inhibitor CFTRi-172, but not by the Ca2+-activated Cl- channel inhibitor DIDS. Furthermore, both forskolin, an agonist of adenylate cyclase (AC) and MDL-12330A, an antagonist of AC could block FA-induced ISC. ConclusionOur results suggest that FA-induced epithelial ISC response is mediated by nerve, involving the activation of TRPV-1 and release of adrenalin as well as substance P.