Here I summarize our PKA studies. Our laboratory has discovered ethanol-induced changes in cAMP signaling in neural cells in culture and in circulating cells from alcoholics.
Ethanol inhibits a specific nucleoside uptake system.
A nucleoside transporter KO mouse is now being prepared in collaboration with Robert Messing. Ethanol inhibition of adenosine uptake increases extracellular adenosine levels, which activates adenosine receptors. After prolonged exposure to ethanol it takes 12-16 hours after ethanol withdrawal for PKA C a to leave the nucleus and return to the Golgi. The molecular events that mediate prolonged PKA C a translocation are under active study. We are investigating the possibility that PKA C a is retained in the nucleus for long periods of time because chronic ethanol promotes the synthesis of a special intranuclear binding protein, which, in part, maintains intranuclear localization of PKA C a .