Regulation of K(+) current in human airway epithelial cells by exogenous and autocrine adenosine.
The regulatory actions of adenosine on ion channel function are mediated by four distinct membrane receptors. The concentration of adenosine in the vicinity of these receptors is controlled, in part, by inwardly directed nucleoside transport. The purpose of this study was to characterize the effects of adenosine on ion channels in A549 cells and the role of nucleoside transporters in this regulation. Ion replacement and pharmacological studies showed that adenosine and an inhibitor of human equilibrative nucleoside transporter (hENT)-1, nitrobenzylthioinosine, activated K(+) channels, most likely Ca(2+)-dependent intermediate-conductance K(+) (I(K)) channels. A(1) but not A(2) receptor antagonists blocked the effects of adenosine. RT-PCR studies showed that A549 cells expressed mRNA for I(K)-1 channels as well as A(1), A(2A), and A(2B) but not A(3) receptors. Similarly, mRNA for equilibrative (hENT1 and hENT2) but not concentrative (hCNT1, hCNT2, and hCNT3) nucleoside transporters was detected, a result confirmed in functional uptake studies. These studies showed that adenosine controls the function of K(+) channels in A549 cells and that hENTs play a crucial role in this process.
Szkotak
A J
AJ
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Ng
A M
AM
Sawicka
J
J
Baldwin
S A
SA
Man
S F
SF
Cass
C E
CE
Young
J D
JD
Duszyk
M
M
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000345:Affinity Labels / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D019898:Autocrine Communication / Q000502:physiology*; D002460:Cell Line; D016764:Cell Polarity; D003022:Clotrimazole / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014529:Uridine / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D000345:Affinity Labels; D004232:Diuretics; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D006131:Growth Inhibitors; D026901:Membrane Transport Proteins; D015221:Potassium Channels; D011799:Quinazolines; D018047:Receptors, Purinergic P1; C438649:SLC29A1 protein, human; C438654:SLC29A2 protein, human; D014230:Triazoles; D014970:Xanthines; D013868:Thioinosine; C057837:3,7-dimethyl-1-propargylxanthine; D000584:Amiloride; C051360:1,3-dipropyl-8-cyclopentylxanthine; D003022:Clotrimazole; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D013805:Theobromine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium; D014529:Uridine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine