Mechanisms for the inhibition of amiloride-sensitive Na+ absorption by extracellular nucleotides in mouse trachea.
Purinergic stimulation of airway epithelial cells induces Cl- secretion and modulates Na+ absorption by an unknown mechanism. To gain insight into this mechanism, we used a perfused micro-Ussing chamber to assess transepithelial voltage (V(te)) and amiloride-sensitive short-circuit current (I(sc-Amil)) in mouse trachea. Exposure to apical ATP or UTP (each 100 micromol/l) caused a large initial increase in lumen negative V(te) and I(sc), corresponding to a transient Cl- secretion, while basolateral application of ATP/UTP induced only a small secretory response. Luminal, but not basolateral, application of nucleotides was followed by a sustained and reversible inhibition of I(sc-Amil) that was independent of extracellular Ca2+ or activation of protein kinase C and was not induced by carbachol (100 micromol/l) or the Ca2+ ionophore ionomycin (1 micromol/l). Removal of extracellular Cl- or exposure to 200 microM DIDS reduced UTP-mediated inhibition of I(sc-Amil) substantially. The phospholipase inhibitor U73122 (10 micromol/l) and pertussis toxin (PTX; 200 ng/ml) both attenuated UTP-induced Cl- secretion and inhibition of I(sc-Amil). Taken together, these data imply a contribution of Cl- conductance and PTX-sensitive G proteins to nucleotide-dependent inhibition of the amiloride-sensitive Na+ current in the mouse trachea.
Kunzelmann
Karl
K
Department of Physiology and Pharmacology, University of Queensland, St. Lucia, QLD 4072, Brisbane, Australia. kunzelmann@mailbox.uq.edu.au
Schreiber
Rainer
R
Cook
David
D
D000042:Absorption; D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009711:Nucleotides / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism
D018118:Chloride Channels; D002712:Chlorides; D004232:Diuretics; D018721:Muscarinic Agonists; D009711:Nucleotides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; D000255:Adenosine Triphosphate; D002217:Carbachol; D012964:Sodium; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium; D014544:Uridine Triphosphate