Inhibition of adenosine uptake by ethanol is specific for one class of nucleoside transporters.
Adenosine uptake via nucleoside transporters is inhibited when S49 and NG108-15 cell lines cells are exposed to ethanol. This inhibition leads to an accumulation of extracellular adenosine that binds to adenosine A2 receptors and increases cAMP production. Subsequently, there is a heterologous desensitization of receptors coupled to adenylyl cyclase for which adenosine also is required. There are multiple classes of facilitative and concentrative nucleoside transporters that could be inhibited by ethanol to initiate this cascade of events. In this paper, we establish that adenosine uptake by only one type of nucleoside transporter, an NBMPR-sensitive facilitative transporter, is inhibited by ethanol. There is no effect on other classes of nucleoside transporters even when present in the same cell. Thus, ethanol-induced extracellular accumulation of adenosine results specifically from inhibition of NBMPR-sensitive facilitative nucleoside transporters. We also find that human lymphocytes express only facilitative nucleoside transporters and that the NBMPR-sensitive type is predominant. Thus, inhibition of this type of transporter by ethanol may be related to the desensitization of cAMP signal transduction that we have reported in lymphocytes from alcoholics.
Krauss
S W
SW
Ernest Gallo Clinic, University of California, San Francisco 94143.
Ghirnikar
R B
RB
Diamond
I
I
Gordon
A S
AS
D000241:Adenosine / Q000097:blood*; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001798:Blood Proteins / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005573:Formycins / Q000097:blood; D005971:Glutamates / Q000097:blood; D018698:Glutamic Acid; D006801:Humans; D066298:In Vitro Techniques; D007532:Isoleucine / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D033703:Nucleoside Transport Proteins; D012964:Sodium / Q000097:blood; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
D001798:Blood Proteins; D002352:Carrier Proteins; D005573:Formycins; D005971:Glutamates; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D007532:Isoleucine; D000431:Ethanol; D018698:Glutamic Acid; D013868:Thioinosine; C034550:formycin; D012964:Sodium; C001789:4-nitrobenzylthioinosine; D000241:Adenosine