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

Abstract

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 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 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 I SC.ConclusionOur 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.

Simulation of Cl− Secretion in Epithelial Tissues: New Methodology Estimating Activity of Electro-Neutral Cl− Transporter

“…The time course of decrease is same as that at the declining phase of Cl − secretion following a transient increase, although shows no instantaneous change just after a change in G A (see Figures 3B,C ). A similar phenomenon is observed in Cl − secretion in cells treated with formaldehyde, bile acids, or Pasteurella multocida toxin (Hennig et al, 2008 ; Ao et al, 2013 ; Luo et al, 2013 ), suggesting that formaldehyde, bile acids, or Pasteurella multocida toxin would activate the apical and basolateral Cl − channels in the same level .…”

“…Many compounds show various time-dependent patterns in stimulation of transcellular Cl − secretion in epithelial cells (Niisato et al, 1999 ; Hennig et al, 2008 ; Ao et al, 2013 ; Luo et al, 2013 ). Transcellular Cl − secretion in epithelial cells is mediated by uptake and release of Cl − into and from the intracellular space.…”

Regulation of smooth muscle contractility by the epithelium in rat tracheas: role of prostaglandin E2 induced by the neurotransmitter acetylcholine

“…Rat tracheal epithelial cells were cultured with a modified procedure, as previously described (22). In brief, the tracheas were isolated and bathed in Hank's balanced salt solution.…”