title: Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca2+-Dependent Manner.
abstract: BACKGROUND
  Phosphorylation state of dopamine- and cAMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP32) is crucial to understand drug-mediated synaptic plasticity. In this study, mechanisms underlying repeated cocaine-stimulated phosphorylation of DARPP32 at threonine 75 (pDARPP32-Thr75) were determined by investigating the hypothesis that activation of protein kinases and phosphatases coupled to glutamate signaling is necessary for the regulation of pDARPP32-Thr75 after repeated cocaine administration.
  
  
  METHODS
  Intracaudate drug infusions into the rat dorsal striatum followed by Western immunoblot analysis were mainly performed to test this hypothesis.
  
  
  RESULTS
  The results demonstrated that 7 repeated daily intraperitoneal injections of cocaine (20mg/kg) upregulated the expression of pDARPP32-Thr75. Increases in the cytosolic Ca(2+) concentrations followed by Ca(2+)-dependent protein kinase activation through stimulation of Ca(2+) channels in striatal neurons were necessary for the phosphorylation. Activation of protein phosphatases further regulated the phosphorylation state by deactivating pDARPP32-Thr75 and upstream protein kinases.
  
  
  CONCLUSIONS
  These findings suggest that activation of protein kinases and phosphatases coupled to glutamate receptors controls the phosphorylation state of DARPP32-Thr75 after repeated exposure to cocaine in the dorsal striatum in a Ca(2+)-dependent manner.
authors.affiliation: Department of Biological Sciences, Pusan National University, Pusan, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Pusan National University, Pusan, Korea.
authors.forename: In Soo
authors.initials: IS
authors.lastname: Ryu
authors.affiliation: Department of Biological Sciences, Pusan National University, Pusan, Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Seo
authors.affiliation: Department of Biological Sciences, Pusan National University, Pusan, Korea. eschoe@pusan.ac.kr.
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Choe
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D002413:Cations, Divalent; D000697:Central Nervous System Stimulants; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D017470:Receptors, Glutamate; D015222:Sodium Channels; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D003042:Cocaine; D002118:Calcium
keywords: DARPP32; glutamate; phosphorylation and dephosphorylation; psychostimulant; striatum