PMID- 23896526
OWN - NLM
STAT- MEDLINE
DCOM- 20140515
LR  - 20130930
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 552
DP  - 2013 Sep 27
TI  - Single or combined treatment with L-DOPA and quinpirole differentially modulate 
      expression and phosphorylation of key regulatory kinases in neuroblastoma cells.
PG  - 168-73
LID - S0304-3940(13)00669-1 [pii]
LID - 10.1016/j.neulet.2013.07.023 [doi]
AB  - In the past decades, the clinical use of dopamine agonists has expanded from 
      adjunct therapy in patients with a deteriorating response to 
      L-3,4-dihydroxyphenylalanine (L-DOPA) to monotherapy for the treatment of early 
      PD. Dopamine agonists provide their antiparkinsonian benefit through stimulation 
      of brain postsynaptic type 2 dopamine receptors that exert their effect through 
      classical cAMP-dependent mechanisms, as well as cAMP-independent cellular 
      signaling cascades, including the Akt/glycogen synthase kinase 3 (GSK3) pathway. 
      Alterations of Akt/GSK3 have been observed and may contribute to the 
      neurodegenerative processes and the development of L-DOPA-induced dyskinesia. The 
      effects L-DOPA and quinpirole, a dopamine agonist, on the two key regulatory 
      kinases, Akt and GSK3, were evaluated in neuroblastoma cell line. L-DOPA and 
      dopamine agonist dose-dependently and differentially modulated Akt and GSK3 
      expression and phosphorylation when added alone or combined. The combined 
      treatment inverted or potentiated the modulatory properties of the single 
      compound. The drug- and concentration-dependent balance of dopamine receptor 
      stimulation over auto-oxidation may distinctively modulate GSK3 isoforms and Akt. 
      Our results indicate that particular attention must be given to drug 
      concentration and combination when multiple therapies are applied for the 
      clinical treatment of PD patients.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Fuzzati-Armentero, Marie Therese
AU  - Fuzzati-Armentero MT
AD  - Laboratory of Functional Neurochemistry, C. Mondino National Neurological 
      Institute, via Mondino 2, Pavia, Italy. Electronic address: 
      marie.armentero@mondino.it.
FAU - Ghezzi, Cristina
AU  - Ghezzi C
FAU - Nistico, Robert
AU  - Nistico R
FAU - Oda, Adriano
AU  - Oda A
FAU - Blandini, Fabio
AU  - Blandini F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130726
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Dopamine Agonists)
RN  - 20OP60125T (Quinpirole)
RN  - 46627O600J (Levodopa)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 2.7.11.26 (glycogen synthase kinase 3 alpha)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Dopamine Agonists/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Humans
MH  - Levodopa/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Quinpirole/*pharmacology
OTO - NOTNLM
OT  - 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
OT  - Akt
OT  - DA
OT  - DR
OT  - Dopamine agonists
OT  - GSK3
OT  - L-3,4-dihydroxyphenylalanine
OT  - MTT
OT  - Neurodegeneration
OT  - PD
OT  - Parkinson's disease
OT  - SH-SY5Y cells
OT  - SNc
OT  - dopamine
OT  - dopamine receptor
OT  - glycogen synthase kinase 3
OT  - l-DOPA
OT  - substantia nigra pars compacta
EDAT- 2013/07/31 06:00
MHDA- 2014/05/16 06:00
CRDT- 2013/07/31 06:00
PHST- 2013/05/06 00:00 [received]
PHST- 2013/06/30 00:00 [revised]
PHST- 2013/07/18 00:00 [accepted]
PHST- 2013/07/31 06:00 [entrez]
PHST- 2013/07/31 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
AID - S0304-3940(13)00669-1 [pii]
AID - 10.1016/j.neulet.2013.07.023 [doi]
PST - ppublish
SO  - Neurosci Lett. 2013 Sep 27;552:168-73. doi: 10.1016/j.neulet.2013.07.023. Epub 
      2013 Jul 26.