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 Citations (Scopus)

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 2000

Fingerprint

Street Drugs
Basal Ganglia
Phosphorylation
Phospho-Specific Antibodies
Corpus Striatum
Protein Phosphatase 2
Dopamine D1 Receptors
Dopamine Agents
Methamphetamine
cyclic AMP-regulated phosphoprotein ARPP-21
Phosphoprotein Phosphatases
Phosphoproteins
Gene Deletion
Cocaine
Cyclic AMP
Dopamine
Neurons

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia. / Caporaso, Gregg L.; Bibb, James A.; Snyder, Gretchen L.; Valle, Carmina; Rakhilin, Sergey; Fienberg, Allen A.; Hemmings, Hugh C.; Nairn, Angus C.; Greengard, Paul.

In: Neuropharmacology, Vol. 39, No. 9, 08.2000, p. 1637-1644.

Research output: Contribution to journalArticle

Caporaso, GL, Bibb, JA, Snyder, GL, Valle, C, Rakhilin, S, Fienberg, AA, Hemmings, HC, Nairn, AC & Greengard, P 2000, 'Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia', Neuropharmacology, vol. 39, no. 9, pp. 1637-1644. https://doi.org/10.1016/S0028-3908(99)00230-0
Caporaso, Gregg L. ; Bibb, James A. ; Snyder, Gretchen L. ; Valle, Carmina ; Rakhilin, Sergey ; Fienberg, Allen A. ; Hemmings, Hugh C. ; Nairn, Angus C. ; Greengard, Paul. / Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia. In: Neuropharmacology. 2000 ; Vol. 39, No. 9. pp. 1637-1644.
@article{ae476c3f6e4343a8b135ac81db575460,
title = "Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia",
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.",
keywords = "Cocaine, Cyclic AMP-dependent protein kinase, Methamphetamine, Phosphoprotein, Phosphorylation state-specific antibody, Protein phosphatase",
author = "Caporaso, {Gregg L.} and Bibb, {James A.} and Snyder, {Gretchen L.} and Carmina Valle and Sergey Rakhilin and Fienberg, {Allen A.} and Hemmings, {Hugh C.} and Nairn, {Angus C.} and Paul Greengard",
year = "2000",
month = "8",
doi = "10.1016/S0028-3908(99)00230-0",
language = "English (US)",
volume = "39",
pages = "1637--1644",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "9",

}

TY - JOUR

T1 - Drugs of abuse modulate the phosphorylation of ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in the basal ganglia

AU - Caporaso, Gregg L.

AU - Bibb, James A.

AU - Snyder, Gretchen L.

AU - Valle, Carmina

AU - Rakhilin, Sergey

AU - Fienberg, Allen A.

AU - Hemmings, Hugh C.

AU - Nairn, Angus C.

AU - Greengard, Paul

PY - 2000/8

Y1 - 2000/8

N2 - 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.

AB - 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.

KW - Cocaine

KW - Cyclic AMP-dependent protein kinase

KW - Methamphetamine

KW - Phosphoprotein

KW - Phosphorylation state-specific antibody

KW - Protein phosphatase

UR - http://www.scopus.com/inward/record.url?scp=0034029747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034029747&partnerID=8YFLogxK

U2 - 10.1016/S0028-3908(99)00230-0

DO - 10.1016/S0028-3908(99)00230-0

M3 - Article

C2 - 10854908

AN - SCOPUS:0034029747

VL - 39

SP - 1637

EP - 1644

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 9

ER -