Published ahead of print on September 11, 2003, doi:10.1165/rcmb.2003-0183OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0183OC Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway EpitheliaDivision of Respiratory Diseases, Department of Internal Medicine, and Department of Cellular Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan Address correspondence to: Yasushi Ito, M.D., Division of Respiratory Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. 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, ADPßS, and ATP
Abbreviations: adenylate cyclase, AC • 1,2-bis (o-amino-phenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, BAPTA-AM • intracellular Ca2+ concentration, [Ca2+]i • cystic fibrosis transmembrane conductance regulator, CFTR • charybdotoxin, ChTx • diacylglycerols, DAG • human intermediate conductance, inward-rectifying Ca2+-activated K+ channel, hIK-1 channel • apical Cl- current, ICl • basolateral K+ current, IK • short-circuit current, Isc • Ca2+-activated K+ channel, KCa channel • 5-nitro-2-(3-phenylpropylamino)-benzoate, NPPB • phosphate-buffered saline, PBS • phosphatidylcholine-phospholipase C, PC-PLC • potential difference, PD • phosphatidylinositol-phospholipase C, PI-PLC • protein kinase C, PKC • physiologic saline solution, PSS • transepithelial resistance, Rt • uridine 5'-triphosphate, UTP This article has been cited by other articles:
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S. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH3) were without any effect on the bilateral ATP-induced Isc, which were, in contrast, attenuated by a phosphatidylcholine-phospholipase C inhibitor (D609) and an adenylate cyclase inhibitor (SQ22536). The responses to ATP from either aspect were also sensitive to an intracellular Ca2+ chelator, 1,2-bis (o-amino-phenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, or a Ca2+-activated K+ channel 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 rather than the apical Cl- current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y1 receptors couple with both phosphatidylcholine-phospholipase C and adenylate cyclase, leading to Cl- secretion, whose rate is essentially regulated by the Ca2+-activated K+ channel–mediated K+ conductance. This suggests the importance of this channel in airway mucociliary clearance. 
