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Vol. 59, Issue 1, 153-160, January 2001

Ethanol Acts Synergistically with a D2 Dopamine Agonist to Cause Translocation of Protein Kinase C

Adrienne S. Gordon, Lina Yao, Zhan Jiang, C. Simone Fishburn,1 Sara Fuchs,2 and Ivan Diamond

Ernest Gallo Clinic and Research Center (A.S.G., L.Y., Z.J., I.D.), Departments of Neurology (A.S.G., L.Y., I.D.), Cellular and Molecular Pharmacology (A.S.G., I.D.), and Neuroscience Graduate Program and Center for the Neurobiology of Addiction (A.S.G., I.D.), University of California, San Francisco, California; and Departments of Biological Chemistry (C.S.F.) and Immunology (S.F.), Weizmann Institute of Science, Rehovot, Israel (C.S.F., S.F.)

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.

1 Current address: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450.

2 This work was carried out while S.F. was on sabbatical leave at the Ernest Gallo Clinic and Research Center.

Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics