Abstract
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.
Footnotes
- Received August 17, 2000.
- Accepted September 22, 2000.
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Send reprint requests to: Adrienne S. Gordon, Ph.D., Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite 200, Emeryville, CA 94608. E-mail:adrienn{at}itsa.ucsf.edu
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↵1 Current address: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450.
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↵2 This work was carried out while S.F. was on sabbatical leave at the Ernest Gallo Clinic and Research Center.
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This research was supported by National Institutes of Health Grants AA10030 and AA10039 to A.S.G. and I.D.; by the Irwin Green Research Fund in Neurosciences; and the Leo and Julia Forchheimer Center for Molecular Genetics at the Weizmann Institute of Science (S.F.).
- The American Society for Pharmacology and Experimental Therapeutics
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