Apical and basolateral ATP-induced anion secretion in polarized human airway epithelia

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 ATRgammaS. 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-phospholipaseC inhibitor (13609) and an adenylate cyclase inhibitor (SQ22536). The responses to ATP from either aspect were also sensitive to an intracellular Call 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 Call 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.