title: Apical and basolateral ATP-induced anion secretion in polarized human airway epithelia.
abstract: 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.
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Son
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ito
authors.forename: Shinji
authors.initials: S
authors.lastname: Sato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakayama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Shimokata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kume
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000067956:Adenylyl Cyclase Inhibitors; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016764:Cell Polarity; D018999:Charybdotoxin / Q000494:pharmacology; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009636:Norbornanes; D010713:Phosphatidylcholines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D001952:Bridged-Ring Compounds; C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D004791:Enzyme Inhibitors; D009636:Norbornanes; C546382:P2RY1 protein, human; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010742:Phospholipid Ethers; D024681:Potassium Channels, Calcium-Activated; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013859:Thiocarbamates; D013871:Thiones; D018999:Charybdotoxin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C017759:9-(tetrahydro-2-furyl)-adenine; C026659:edelfosine; C046498:tricyclodecane-9-yl-xanthogenate; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D000225:Adenine; D011188:Potassium; D002118:Calcium