Metabotropic receptors in excitotoxicity: (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) protects against rat striatal quinolinic acid lesions.

Academic Article

Abstract

  • Striatal quinolinate lesions mimic many of the neuropathological characteristics of Huntington's disease. This excitotoxicity is mediated by combined activity of N-methyl-D-aspartate and metabotropic glutamate receptors (mGluRs). Using recently developed phenylglycine derivatives, (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) and (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG), we investigated the role of the different sub-classes of mGluRs in the in vivo excitotoxic process. (S)-4C3HPG (500 and 1000 nmol), co-injected with quinolinic acid, significantly reduced lesion volumes by 52 and 89%, respectively, whereas the same doses of (+)-MCPG had no effect on lesion size. The differential actions of these two drugs at Group 1 and Group 2 metabotropic receptors may explain their differential effects. These observations confirm the important role of mGluRs in excitotoxicity and identify them as promising targets for intervention.
  • Published In

    Keywords

  • Animals, Benzoates, Dose-Response Relationship, Drug, Excitatory Amino Acid Antagonists, Glycine, Male, Neostriatum, Neurons, Neuroprotective Agents, Neurotoxins, Quinolinic Acid, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate
  • Author List

  • Orlando LR; Standaert DG; Penney JB; Young AB
  • Start Page

  • 109
  • End Page

  • 112
  • Volume

  • 202
  • Issue

  • 1-2