ATP-induced Cl- secretion with suppressed Na+ absorption in rabbit tracheal epithelium.
The effect of extracellular ATP on ion transport of rabbit tracheal epithelium was examined using an Ussing chamber. Isoproterenol (10(-8)-10(-5) M) did not alter the electrophysiological properties across the tracheal epithelium. Apically applied ATP induced an initial transient increase in short circuit current (SCC) followed by a decline to below the prior baseline. The initial increase by ATP (10(-4) M) was significantly inhibited by a Cl(-) -channel inhibitor diphenylamine-2-carboxylate (DPC, 5 x 10(-4) M) and Cl(-) -substitution with gluconate in the bath solution, while a cystic fibrosis transmembrane regulator (CFTR) Cl(-) -channel inhibitor glibenclamide (10(-4) M), a Na(+)-channel inhibitor amiloride (10(-4) M) and a K(+) -channel inhibitor quinidine (10(-4) M) all failed to alter it. The decline in SCC by ATP was abolished by amiloride, while DPC or Cl-substitution with gluconate in the bath solution did not alter it. Ca(2+)-removal from the bath solutions did not significantly alter the initial increase nor the decline by ATP. Ionomycin (10(-5) M) induced an initial transient increase in SCC, to a degree similar to that by ATP alone. A calmodulin antagonist W-7 reduced the SCC baseline and abolished SCC increase by ATP. These findings indicate that ATP activates Ca(2+)-dependent Cl(-) -channels with an inhibition of Na -channel activity or absorption in rabbit tracheal epithelium.
Iwase
N
N
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Sasaki
T
T
Shimura
S
S
Yamamoto
M
M
Suzuki
S
S
Shirato
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D018118:Chloride Channels; D007202:Indicators and Reagents; D015222:Sodium Channels; D000255:Adenosine Triphosphate; D007545:Isoproterenol; D002118:Calcium