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Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia.

TitleDrugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia.
Publication TypeJournal Article
Year of Publication2000
AuthorsCaporaso GL, Bibb JA, Snyder GL, Valle C, Rakhilin S, Fienberg AA, Hemmings HC, Nairn AC, Greengard P
Date Published2000 Jul 10
KeywordsAnimals, Antibodies, Monoclonal, Basal Ganglia, Cattle, Cocaine, Corpus Striatum, Cyclosporine, Dopamine and cAMP-Regulated Phosphoprotein 32, Dopamine Uptake Inhibitors, Enzyme Inhibitors, Methamphetamine, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Okadaic Acid, Oxazoles, Phosphoproteins, Phosphorylation, Rats, Street Drugs

ARPP-21 is a cyclic AMP-regulated phosphoprotein of M(r) 21 kDa that is enriched in the cell bodies and terminals of medium-sized spiny neurons in the basal ganglia. Using a new phosphorylation state-specific antibody selective for the detection of ARPP-21 phosphorylated on Ser(55), we have demonstrated that activation of dopamine D1 receptors increased the level of ARPP-21 phosphorylation in mouse striatal slices. Conversely, activation of D2 receptors caused a large decrease in ARPP-21 phosphorylation. Treatment of mice with either methamphetamine or cocaine resulted in increased ARPP-21 phosphorylation in vivo. Studies using specific inhibitors of protein phosphatases and experiments in mice bearing a targeted deletion of the gene for DARPP-32, a dopamine-activated inhibitor of protein phosphatase-1, indicated that protein phosphatase-2A is primarily responsible for dephosphorylation of ARPP-21 in mouse striatum. These results demonstrate that phosphorylation and dephosphorylation of ARPP-21 are tightly regulated in the striatum. We speculate that ARPP-21 might mediate some of the physiologic effects of dopamine and certain drugs of abuse in the basal ganglia.

Alternate JournalNeuropharmacology
PubMed ID10854908
Grant List10044 / / PHS HHS / United States
P01 DA010044 / DA / NIDA NIH HHS / United States