Metabotropic glutamate receptor type 5 in levodopa-induced motor complications.
Metabotropic glutamate receptors type 5 (mGluR5) are implicated in regulation of synaptic plasticity and learning, and were the focus of our investigation in human Parkinson's disease (PD) patients with dyskinesias and wearing-off, and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys with dyskinesias. Using the selective mGluR5 ligand [(3)H]ABP688 autoradiography, we measured mGluR5 in brain slices from 11 normal and 14 PD patients and from MPTP monkeys, in relation to motor complications (dyskinesias and wearing-off) associated with treatment with l-dopa. In 16 monkeys with a bilateral MPTP lesion and four controls, [(3)H]ABP688 specific binding was elevated in the striatum of dyskinetic l-dopa-treated MPTP monkeys but not in MPTP monkeys without dyskinesias compared to controls. PD patients with motor complications (either dyskinesias or wearing-off) had higher [(3)H]ABP688 specific binding compared to those without motor complications and controls in putamen, external and internal globus pallidus. Elevated glutamatergic transmission as measured with increased mGluR5 specific binding was associated with motor complications and its antagonism could be targeted for their treatment.
Ouattara
Bazoumana
B
Molecular Endocrinology and Genomic Research Center, Laval University Medical Center, Quebec (QC), Canada.
Grégoire
Laurent
L
Morissette
Marc
M
Gasparini
Fabrizio
F
Vranesic
Ivo
I
Bilbe
Graeme
G
Johns
Donald R
DR
Rajput
Alex
A
Hornykiewicz
Oleh
O
Rajput
Ali H
AH
Gomez-Mancilla
Baltazar
B
Di Paolo
Thérèse
T
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000633:toxicity; D015331:Cohort Studies; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D018698:Glutamic Acid / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000633:toxicity; D008252:Macaca fascicularis; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D000978:Antiparkinson Agents; C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D007980:Levodopa