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Title: Regulation of adenosine transport by acute and chronic ethanol exposure

Chronic exposure to ethanol results in a desensitization of adenosine receptor-stimulated cAMP production. Since adenosine is released by cells and is known to desensitize its own as well as other receptors, it may be involved in ethanol-induced desensitization of adenosine receptor function. Therefore, we have examine the acute and chronic effects of ethanol on the transport of adenosine via the nucleoside transport. Acute exposure to ethanol caused an inhibition of adenosine uptake in S49 lymphoma cells. This decrease in uptake resulted in accumulation of extracellular adenosine after ethanol exposure. The effect of ethanol was specific to nucleoside transport. Uptake of uridine, also transported by the nucleoside transporter, was inhibited by ethanol to the same degree as adenosine uptake, while neither isoleucine nor deoxyglucose uptake was altered by ethanol treatment. Inhibition of adenosine uptake by ethanol was non-competitive and dependent on the concentration of ethanol. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol. There was no longer an acute inhibition of adenosine uptake, nor was these accumulation of extracellular adenosine. Chronic ethanol exposure also resulted in a decrease in the absolute rate of adenosine uptake. Binding studies using a high affinity lignad for the nucleosidemore » transporter, nitrobenzylthioinosine (NBMPR), indicate that this decreased uptake was due to a decrease in the maximal number of binding sites. These ethanol-induced changes in adenosine transport may be important for the acute and chronic effects of ethanol.« less
Authors:
; ; ;  [1]
  1. (Univ. of California, San Francisco (USA))
Publication Date:
OSTI Identifier:
6832739
Resource Type:
Journal Article
Resource Relation:
Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (USA); Journal Volume: 3:3
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ADENOSINE; BIOCHEMICAL REACTION KINETICS; ETHANOL; TOXICITY; ACUTE EXPOSURE; CHRONIC EXPOSURE; DOSE-RESPONSE RELATIONSHIPS; INHIBITION; TOLERANCE; TUMOR CELLS; ALCOHOLS; ANIMAL CELLS; HYDROXY COMPOUNDS; KINETICS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; REACTION KINETICS; RIBOSIDES 560300* -- Chemicals Metabolism & Toxicology