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 lea ds to an accumulation of extracellular adenosine that binds to adenosi ne A2 receptors and increases cAMP production. Subsequently, there is a heterologous desensitization of receptors coupled to adenylyl cyclas e for which adenosine also is required. There are multiple classes of facilitative and concentrative nucleoside transporters that could be i nhibited by ethanol to initiate this cascade of events. In this paper, we establish that adenosine uptake by only one type of nucleoside tra nsporter, an NBMPR-sensitive facilitative transporter, is inhibited by ethanol. There is no effect on other classes of nucleoside transporte rs even when present in the same cell. Thus, ethanol-induced extracell ular accumulation of adenosine results specifically from inhibition of NBMPR-sensitive facilitative nucleoside transporters. We also find th at 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 desensitiza tion of cAMP signal transduction that we have reported in lymphocytes from alcoholics.