Ethanol acts synergistically with a D2 dopamine agonist to cause translocation of protein kinase C.
Ethanol and other drugs of abuse increase synaptic dopamine levels; however, little is known about how ethanol alters dopaminergic signaling. We have reported that ethanol induces translocation of delta and epsilon protein kinase C (PKC) in neural cells in culture. Using NG108-15 and Chinese hamster ovary cell lines that express the dopamine D2 receptor (D2R), we show here that the D2R agonist R(-)-2,10,11-trihydroxy-N-propyl-noraporphine hydrobromide (NPA) also causes translocation of delta and epsilon PKC to the same sites as ethanol-induced translocation. D2R agonist and ethanol-induced translocation of delta and epsilon PKC share a common pathway that is blocked by pertussis toxin and requires phospholipase C (PLC) activity. These data suggest that both D2R agonists and ethanol activate PLC via a trimeric G protein leading to production of diacylglycerol with subsequent activation and translocation of delta and epsilon PKC. Moreover, ethanol and NPA, when present together at low concentrations that alone are ineffective, act synergistically to cause translocation of delta and epsilon PKC. Our data suggest that ethanol causes translocation of delta and epsilon PKC but cells expressing the D2R, such as neurons in the nucleus accumbens, may be particularly sensitive to low concentrations of ethanol.
Gordon
A S
AS
Ernest Gallo Clinic and Research Center, Emeryville, California 94608, USA. adrienn@itsa.ucsf.edu
Yao
L
L
Jiang
Z
Z
Fishburn
C S
CS
Fuchs
S
S
Diamond
I
I
D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D002492:Central Nervous System Depressants / Q000494:pharmacology; D006224:Cricetinae; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D002492:Central Nervous System Depressants; D007527:Isoenzymes; D017448:Receptors, Dopamine D2; D000431:Ethanol; C044756:10,11-dimethoxy-N-n-propylnoraporphine; C497259:Prkcd protein, mouse; C497260:Prkcd protein, rat; C497256:Prkce protein, mouse; C497257:Prkce protein, rat; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D010738:Type C Phospholipases; D001058:Apomorphine