Effects of ethanol-induced changes in adenosine transport on cAMP production in rat hepatocytes

Ethanol-induced increases in extracellular adenosine in primary cultures of rat hepatocytes are due to inhibition of adenosine uptake via the nucleoside transporter, as well as increased adenosine production resulting from ethanol metabolism. Chronic treatment of hepatocytes with ethanol during culture increases receptor-stimulated cAMP production. This increase is due, at least in part, to a decrease in Gi mediated inhibition of cAMP production and can be prevented by co-culture with the adenosine A1 receptor antagonist, cyclopentyltheophylline. These data suggest that increased extracellular adenosine, acting via adenosine A1 receptors, mediates the chronic effects of ethanol on cAMP in hepatocytes.