title: Chloride secretory response to extracellular ATP in human normal and cystic fibrosis nasal epithelia.
abstract: Chloride secretion across cystic fibrosis (CF) airway epithelia is effectively regulated by pathways associated with intracellular Ca2+ metabolism, but not by mechanisms dependent on protein kinase A or C. In a search for therapeutically useful agonists, we investigated the effects of extracellular ATP on the Cl- secretory process in human normal and CF nasal epithelial cultures with double-barreled Cl- selective microelectrodes. When applied to the basolateral membrane of normal, but not CF, nasal epithelium, extracellular ATP (10(-4) M) stimulated a small increase in Cl- secretion that was primarily associated with a hyperpolarizing conductance in the basolateral membrane. In contrast, ATP applied to the apical (luminal) membrane of either normal or CF nasal epithelium stimulated a greater increase in Cl- secretion that was associated with activation of an apical membrane Cl- conductance. The increases in Cl- current and apical conductance were greater in CF tissues and attained maximal values similar to normal nasal epithelium. We conclude 1) that basolateral application of ATP indirectly induces Cl- secretion by activating a basolateral (K+) conductance and is an effective secretagogue only in normal nasal epithelium and 2) that luminally applied ATP is an effective Cl- secretagogue that activates the apical membrane Cl- conductance of normal and CF nasal epithelia to an equivalent level.
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill 27599-7020.
authors.forename: L L
authors.initials: LL
authors.lastname: Clarke
authors.forename: R C
authors.initials: RC
authors.lastname: Boucher
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000328:Adult; D002712:Chlorides / Q000378:metabolism*; D046508:Culture Techniques; D003550:Cystic Fibrosis / Q000378:metabolism*; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism* / Q000502:physiology; D012016:Reference Values
chemical_list: D002712:Chlorides; D000255:Adenosine Triphosphate