Metabotropic glutamate receptor II in the brains of Parkinsonian patients.

Abstract

Modulation of basal ganglia group II metabotropic glutamate receptors (mGluR2/3) is a potential therapeutic alternative to levodopa in Parkinson disease (PD). We used receptor-binding autoradiography of the mGluR2/3-selective radioligand [H]LY341495 in postmortem brain specimens from PD patients (n = 14) and controls (n=11) to investigate possible contributions of changes in ligand binding of this receptor to levodopa-associated motor complications experienced premortem in PD patients. The PD patients included those with and without histories of dyskinesias and those with and without "wearing off," which is defined as a reduced period of benefit from levodopa. Specific binding of [H]LY341495 to mGluR2/3 in the basal ganglia was higher in the caudate nucleus than the putamen and lower by approximately half in the external and internal globus pallidus (GPi) in controls. [H]LY341495-specific binding was reduced in the caudate and GPi in patients without wearing-off (-22% caudate, -30% GPi), compared with controls and with patients who had experienced wearing-off; there were no differences among PD patients with or without dyskinesias. These data suggest that an adaptive downregulation of mGluR2/3 in PD patients without wearing-off may compensate for increased glutamate. They indicate a key role for mGluR2/3 in control of movement and the potential for mGluR2/3-targeted drugs in the management of wearing-off fluctuations in PD.

• Authors: Pershia Samadi, Alex Rajput, Frédéric Calon, Laurent Grégoire, Oleh Hornykiewicz, Ali H Rajput, Thèrèse Di Paolo
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 68 Issue 4 Pg. 374-82 (Apr 2009) ISSN: 0022-3069 [Print] England
• PMID: 19287314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Antiparkinson Agents
• Excitatory Amino Acid Antagonists
• Iodine Radioisotopes
• LY 341495
• Receptors, Metabotropic Glutamate
• Xanthenes
• metabotropic glutamate receptor 2
• Tritium
• RTI 121
• Levodopa
• Cocaine

Topics

• Aged
• Aged, 80 and over
• Amino Acids (pharmacology)
• Antiparkinson Agents (adverse effects)
• Brain (drug effects, metabolism, pathology)
• Cocaine (analogs & derivatives)
• Dyskinesia, Drug-Induced (etiology, pathology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Female
• Humans
• Iodine Radioisotopes
• Levodopa (adverse effects)
• Male
• Parkinsonian Disorders (drug therapy, pathology)
• Postmortem Changes
• Radioligand Assay
• Receptors, Metabotropic Glutamate (metabolism)
• Tritium (pharmacology)
• Xanthenes (pharmacology)