Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
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Animals
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Anions
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Biological Transport / drug effects
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Capsaicin / analogs & derivatives
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Capsaicin / pharmacology
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Cells, Cultured
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Chlorides / metabolism*
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Colforsin / pharmacology
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Epinephrine / metabolism
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Formaldehyde / pharmacology*
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Imines / pharmacology
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Male
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Nerve Endings / drug effects
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Nerve Endings / metabolism*
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Quinuclidines / pharmacology
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Rats
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Respiratory Mucosa / drug effects
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Respiratory Mucosa / metabolism*
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Substance P / metabolism
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TRPV Cation Channels / agonists
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TRPV Cation Channels / antagonists & inhibitors
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TRPV Cation Channels / metabolism*
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Trachea / drug effects
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Trachea / metabolism*
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ortho-Aminobenzoates / pharmacology
Substances
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Anions
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Chlorides
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Imines
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Quinuclidines
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TRPV Cation Channels
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Trpv1 protein, rat
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ortho-Aminobenzoates
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L 703606
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Colforsin
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Formaldehyde
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Substance P
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RMI 12330A
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fenamic acid
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capsazepine
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
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Capsaicin
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Epinephrine
Grants and funding
This project was supported by the National Key Basic Research Project of China (973 program; No. 2009CB522102 and 2010CB945403), the National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Twelfth Five-year Plan Period (2011ZX09307-304), and the National Natural Science Foundation of China (No. 31071019 and 31271247). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.