L-DOPA reverses the MPTP-induced elevation of the arrestin2 and GRK6 expression and enhanced ERK activation in monkey brain.

Bezard E, Gross CE, Qin L, Gurevich VV, Benovic JL, Gurevich EV
Neurobiol Dis. 2005 18 (2): 323-35

PMID: 15686961 · DOI:10.1016/j.nbd.2004.10.005

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.

MeSH Terms (19)

Animals Antiparkinson Agents Arrestins Basal Ganglia beta-Adrenergic Receptor Kinases Brain Cyclic AMP-Dependent Protein Kinases Disease Models, Animal Extracellular Signal-Regulated MAP Kinases Female G-Protein-Coupled Receptor Kinases Levodopa Macaca fascicularis Parkinsonian Disorders Phosphoproteins Phosphorylation Protein-Serine-Threonine Kinases Receptors, G-Protein-Coupled Up-Regulation

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