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

BACKGROUND: Recent 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 FINDINGS: The 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 I (SC) 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 I (SC) induced by FA. The TRPV-1 agonist capsaicin (Cap) induced an increase of I (SC), which was similar to the I (SC) induced by FA. L-703606, an NK-1 specific inhibitor and propranolol, an adrenalin β receptor inhibitor significantly abolished the I (SC) induced by FA or Cap. In the ion substitute analysis, FA could not induce I (SC) in the absence of extracelluar Cl(-). The I (SC) induced by FA could be blocked by the non-specific Cl(-) channel inhibitor DPC and the CFTR specific inhibitor CFTR(i-172), but not by the Ca(2+)-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 I (SC). CONCLUSION: Our results suggest that FA-induced epithelial I (SC) response is mediated by nerve, involving the activation of TRPV-1 and release of adrenalin as well as substance P.