RT Journal Article
SR Electronic
T1 Ethanol Acts Synergistically with a D2 Dopamine Agonist to Cause Translocation of Protein Kinase C
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 153
OP 160
DO 10.1124/mol.59.1.153
VO 59
IS 1
A1 Gordon, Adrienne S.
A1 Yao, Lina
A1 Jiang, Zhan
A1 Fishburn, C. Simone
A1 Fuchs, Sara
A1 Diamond, Ivan
YR 2001
UL http://molpharm.aspetjournals.org/content/59/1/153.abstract
AB 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 δ and ε 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 agonistR(−)-2,10,11-trihydroxy-N-propyl-noraporphine hydrobromide (NPA) also causes translocation of δ and ε PKC to the same sites as ethanol-induced translocation. D2R agonist and ethanol-induced translocation of δ and ε 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 δ and ε PKC. Moreover, ethanol and NPA, when present together at low concentrations that alone are ineffective, act synergistically to cause translocation of δ and ε PKC. Our data suggest that ethanol causes translocation of δ and ε PKC but cells expressing the D2R, such as neurons in the nucleus accumbens, may be particularly sensitive to low concentrations of ethanol.