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Son M, Ito Y, Sato S, Ishikawa T, Kondo M, Nakayama S, Shimokata K, Kume H: Apical and basolateral ATP-induced anion secretion in polarized human airway epithelia. Am J Respir Cell Mol Biol. 2004 Mar;30(3):411-9. Epub 2003 Sep 11.
The present study investigated mechanisms underlying apical and basolateral P2Y (1)-mediated Cl (-) secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (I (sc)) with different properties via P2Y (1) 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, ADPbetaS, and ATPgammaS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH (3)) were without any effect on the bilateral ATP-induced I (sc), 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 Ca (2+) chelator, 1,2-bis (o-amino-phenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, or a Ca (2+)-activated K (+) channel inhibitor, charybdotoxin, although differential Ca (2+) signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the I (sc) and the basolateral K (+) current rather than the apical Cl (-) current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y (1) receptors couple with both phosphatidylcholine-phospholipase C and adenylate cyclase, leading to Cl (-) secretion, whose rate is essentially regulated by the Ca (2+)-activated K (+) channel-mediated K (+) conductance. This suggests the importance of this channel in airway mucociliary clearance. |
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