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.


RESULTS
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).


CONCLUSIONS
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.
School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Yu-Li
YL
Luo
Hong-Mei
HM
Guo
Yi-Lin
YL
Zhang
Peng-Xiao
PX
Chen
Yun-Xin
YX
Zhu
Jie-Hong
JH
Huang
Wen-Liang
WL
Zhou
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000838:Anions; D001692:Biological Transport / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005557:Formaldehyde / Q000494:pharmacology*; D007097:Imines / Q000494:pharmacology; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000838:Anions; D002712:Chlorides; D007097:Imines; D011812:Quinuclidines; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D062367:ortho-Aminobenzoates; C076851:L 703606; D005576:Colforsin; D005557:Formaldehyde; D013373:Substance P; C014925:RMI 12330A; C001209:fenamic acid; C071423:capsazepine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002211:Capsaicin; D004837:Epinephrine