Aims

To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.

___________________________________________

Wednesday, October 15, 2008

Ethanol Regulation of D1 Dopamine Receptor Signaling is Mediated by Protein Kinase C in an Isozyme-Specific Manner
Neuropsychopharmacology (2008) 33, 2900–2911


Ethanol consumption potentiates dopaminergic signaling that is partially mediated by the D1 dopamine receptor; however, the mechanism(s) underlying ethanol-dependent modulation of D1 signaling is unclear.

We now show that ethanol treatment of D1 receptor-expressing cells decreases D1 receptor phosphorylation and concurrently potentiates dopamine-stimulated cAMP accumulation. Protein kinase C (PKC) inhibitors mimic the effects of ethanol on D1 receptor phosphorylation and dopamine-stimulated cAMP levels in a manner that is non-additive with ethanol treatment. Ethanol was also found to modulate specific PKC activities as demonstrated using in vitro kinase assays where ethanol treatment attenuated the activities of lipid-stimulated PKCitalic gamma and PKCdelta in membrane fractions, but did not affect the activities of PKCalpha, PKCbeta1, or PKCalt epsilon. Importantly, ethanol treatment potentiated D1 receptor-mediated DARPP-32 phosphorylation in rat striatal slices, supporting the notion that ethanol enhances D1 receptor signaling in vivo.

These findings suggest that ethanol inhibits the activities of specific PKC isozymes, resulting in decreased D1 receptor phosphorylation and enhanced dopaminergic signaling.


Read Full Abstract

Request Reprint E-Mail: sibley@helix.nih.gov
_____________________________________________________________
at