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

Gregg L. Caporaso, James A. Bibb, Gretchen L. Snyder, Carmina Valle, Sergey Rakhilin, Allen A. Fienberg, Hugh C. Hemmings, Angus C. Nairn, Paul Greengard

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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 Ser55, 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. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1637-1644
Number of pages8
JournalNeuropharmacology
Volume39
Issue number9
DOIs
StatePublished - Aug 1 2000

Keywords

  • Cocaine
  • Cyclic AMP-dependent protein kinase
  • Methamphetamine
  • Phosphoprotein
  • Phosphorylation state-specific antibody
  • Protein phosphatase

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Caporaso, G. L., Bibb, J. A., Snyder, G. L., Valle, C., Rakhilin, S., Fienberg, A. A., Hemmings, H. C., Nairn, A. C., & Greengard, P. (2000). Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia. Neuropharmacology, 39(9), 1637-1644. https://doi.org/10.1016/S0028-3908(99)00230-0