2-Chloroadenosine, a permeant for the nucleoside transporter.
Human erythrocytes were shown to possess a saturable uptake mechanism for 2-chloroadenosine (apparent Km 23 microM, 22 degrees). Uptake by this route was inhibited by nitrobenzylthioinosine, uridine and adenosine, but adenine had no effect. In addition, uridine caused the countertransport of 2-chloroadenosine and vice versa. 2-Chloroadenosine was also shown to be an apparent competitive inhibitor of uridine influx (apparent Ki value of 33 microM) and high-affinity nitrobenzylthioinosine binding (apparent Ki 0.18 mM). The apparent Ki value for inhibition of uridine influx was close to the apparent Km value for 2-chloroadenosine uptake. Previous studies [Jarvis et al., Biochem. J. 208, 83 (1982)] have demonstrated that dog erythrocytes do not possess a saturable transport system for uridine and adenosine. Similarly, in the present study, the entry of 2-chloroadenosine into dog erythrocytes was slow and linear with concentration. Nitrobenzylthioinosine (NBMPR) had no effect on the uptake of 2-chloroadenosine into dog erythrocytes. These results demonstrate that 2-chloroadenosine enters human erythrocytes by the same nucleoside carrier as other nucleosides. It is suggested from these data that the previous explanation that the inability of nucleoside transport inhibitors to potentiate the pharmacological effects of 2-chloroadenosine was due to the failure of the nucleoside carrier to accept 2-chloroadenosine as a permeant may have to be reassessed.
D015762:2-Chloroadenosine; D000225:Adenine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D033703:Nucleoside Transport Proteins; D013868:Thioinosine / Q000031:analogs & derivatives / Q000097:blood; D014529:Uridine / Q000097:blood / Q000494:pharmacology
D001798:Blood Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D015762:2-Chloroadenosine; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D000225:Adenine; D000241:Adenosine; D014529:Uridine