Dataset Information

Cellular mechanism underlying formaldehyde-stimulated Cl- secretion in rat airway epithelium.

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 ? 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.

SUBMITTER: Luo YL

PROVIDER: S-EPMC3553115 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Cellular mechanism underlying formaldehyde-stimulated Cl- secretion in rat airway epithelium.

Luo Yu-Li YL Guo Hong-Mei HM Zhang Yi-Lin YL Chen Peng-Xiao PX Zhu Yun-Xin YX Huang Jie-Hong JH Zhou Wen-Liang WL

PloS one 20130123 1

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 i ...[more]

PMID: 23372735

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Project description:The vestibular system controls the ion composition of its luminal fluid through several epithelial cell transport mechanisms under hormonal regulation. The semicircular canal duct (SCCD) epithelium has been shown to secrete Cl- under ?2-adrenergic stimulation. In the current study, we sought to determine the ion transporters involved in Cl- secretion and whether secretion is regulated by PKA and glucocorticoids.Short circuit current (Isc) from rat SCCD epithelia demonstrated stimulation by forskolin (EC50: 0.8 ?M), 8-Br-cAMP (EC50: 180 ?M), 8-pCPT-cAMP (100 ?M), IBMX (250 ?M), and RO-20-1724 (100 ?M). The PKA activator N6-BNZ-cAMP (0.1, 0.3 & 1 mM) also stimulated Isc. Partial inhibition of stimulated Isc individually by bumetanide (10 & 50 ?M), and [(dihydroindenyl)oxy]alkanoic acid (DIOA, 100 ?M) were additive and complete. Stimulated Isc was also partially inhibited by CFTRinh-172 (5 & 30 ?M), flufenamic acid (5 ?M) and diphenylamine-2,2'-dicarboxylic acid (DPC; 1 mM). Native canals of CFTR+/- mice showed a stimulation of Isc from isoproterenol and forskolin+IBMX but not in the presence of both bumetanide and DIOA, while canals from CFTR-/- mice had no responses. Nonetheless, CFTR-/- mice showed no difference from CFTR+/- mice in their ability to balance (rota-rod). Stimulated Isc was greater after chronic incubation (24 hr) with the glucocorticoids dexamethasone (0.1 & 0.3 ?M), prednisolone (0.3, 1 & 3 ?M), hydrocortisone (0.01, 0.1 & 1 ?M), and corticosterone (0.1 & 1 ?M) and mineralocorticoid aldosterone (1 ?M). Steroid action was blocked by mifepristone but not by spironolactone, indicating all the steroids activated the glucocorticoid, but not mineralocorticoid, receptor. Expression of transcripts for CFTR; for KCC1, KCC3a, KCC3b and KCC4, but not KCC2; for NKCC1 but not NKCC2 and for WNK1 but only very low WNK4 was determined.These results are consistent with a model of Cl- secretion whereby Cl- is taken up across the basolateral membrane by a Na+-K+-2Cl- cotransporter (NKCC) and potentially another transporter, is secreted across the apical membrane via a Cl- channel, likely CFTR, and demonstrate the regulation of Cl- secretion by protein kinase A and glucocorticoids.

Dataset Information

Cellular mechanism underlying formaldehyde-stimulated Cl- secretion in rat airway epithelium.

Background

Methodology/principal findings

Conclusion

Publications

Cellular mechanism underlying formaldehyde-stimulated Cl- secretion in rat airway epithelium.

Similar Datasets

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