Abstract: | The regulatory actions ofadenosine on ion channel function are mediated by four distinctmembrane receptors. The concentration of adenosine in the vicinity ofthese receptors is controlled, in part, by inwardly directed nucleosidetransport. The purpose of this study was to characterize the effects ofadenosine on ion channels in A549 cells and the role of nucleosidetransporters in this regulation. Ion replacement and pharmacologicalstudies showed that adenosine and an inhibitor of human equilibrative nucleoside transporter (hENT)-1, nitrobenzylthioinosine, activated K+ channels, most likely Ca2+-dependentintermediate-conductance K+ (IK)channels. A1 but not A2 receptor antagonistsblocked the effects of adenosine. RT-PCR studies showed that A549 cellsexpressed mRNA for IK-1 channels as well asA1, A2A, and A2B but notA3 receptors. Similarly, mRNA for equilibrative (hENT1 andhENT2) but not concentrative (hCNT1, hCNT2, and hCNT3) nucleosidetransporters was detected, a result confirmed in functional uptakestudies. These studies showed that adenosine controls the function ofK+ channels in A549 cells and that hENTs play a crucialrole in this process. |