Published ahead of print on September 11, 2003, doi:10.1165/rcmb.2003-0183OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 3, March 2004, 411-419 A more recent version of this article appeared on March 1, 2004
Submitted on May 8, 2003 Apical and Basolateral ATP-induced Anion Secretion in Polarized Human Airway EpitheliaMasami Son1,1 Division of Respiratory Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan, 2 Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan * To whom correspondence should be addressed. E-mail: itoyasu{at}med.nagoya-u.ac.jp.
The present study investigated mechanisms underlying apical and basolateral P2Y1-mediated Cl- secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (Isc) with different properties via P2Y1 receptors. The former comprised an immediate rise followed by a slow attenuation, whereas the latter was a transient rise with a higher peak and shorter duration (< 2 min). The actions of ATP were simulated by those of ADP, ADP
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S and ATP
S. Antagonists of PI-PLC (U73122, ET-18-OCH3) were without any effect on the bilateral ATP-induced Isc which were, in contrast, attenuated by a PC-PLC inhibitor (D609) and an adenylate cyclase inhibitor (SQ22536). The responses to ATP from either aspect were also sensitive to an intracellular Ca2+ chelator, BAPTA-AM, or a Ca2+-activated K+ channel (hIK-1) inhibitor, charybdotoxin, although differential Ca2+ signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the Isc and the basolateral K+ current (IK) rather than the apical Cl- current (ICl) under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y1 receptors couple with both PC-PLC and adenylate cyclase, leading to Cl- secretion whose rate is essentially regulated by the hIK-1-mediated K+ conductance. This suggests the importance of this channel in airway mucociliary clearance.
