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, ADPβS, and ATP-γS. 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 Ca 2+-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 Ca 2+-activated K+ channel-mediated K+ conductance. This suggests the importance of this channel in airway mucociliary clearance.
|ジャーナル||American Journal of Respiratory Cell and Molecular Biology|
|出版物ステータス||Published - 01-03-2004|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology