L-DOPA reverses the MPTP-induced elevation of the arrestin2 and GRK6 expression and enhanced ERK activation in monkey brain.
Neurobiology of Disease. 2005-03-01; 18(2): 323-335
DOI: 10.1016/j.nbd.2004.10.005
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1. Neurobiol Dis. 2005 Mar;18(2):323-35.
L-DOPA reverses the MPTP-induced elevation of the arrestin2 and GRK6 expression
and enhanced ERK activation in monkey brain.
Bezard E(1), Gross CE, Qin L, Gurevich VV, Benovic JL, Gurevich EV.
Author information:
(1)Basal Gang, CNRS UMR 5543, Université Victor Segalen-Bordeaux 2, 33076
Bordeaux Cedex, France.
Dysregulation of dopamine receptors (DARs) is believed to contribute to Parkinson
disease (PD) pathology. G protein-coupled receptors (GPCR) undergo
desensitization via activation-dependent phosphorylation by G protein-coupled
receptor kinases (GRKs) followed by arrestin binding. Using quantitative Western
blotting, we detected profound differences in the expression of arrestin2 and
GRKs among four experimental groups of nonhuman primates: (1) normal, (2)
parkinsonian, (3) parkinsonian treated with levodopa without or (4) with
dyskinesia. Arrestin2 and GRK6 expression was significantly elevated in the
MPTP-lesioned group in most brain regions; GRK2 was increased in caudal caudate
and internal globus pallidus. Neither levodopa-treated group differed
significantly from control. The only dyskinesia-specific change was an elevation
of GRK3 in the ventral striatum of the dyskinetic group. Changes in arrestin and
GRK expression in the MPTP group were accompanied by enhanced ERK activation and
elevated total ERK expression, which were also reversed by L-DOPA. The data
suggest the involvement of arrestins and GRKs in Parkinson disease pathology and
the effects of levodopa treatment.
DOI: 10.1016/j.nbd.2004.10.005
PMID: 15686961 [Indexed for MEDLINE]