Metabotropic glutamate receptor agonists inhibit endogenous glutamate release from rat striatal synaptosomes

Eur J Pharmacol. 1995 Apr 13;277(1):117-21. doi: 10.1016/0014-2999(95)00119-6.

Abstract

A striatal synaptosomal preparation was used to assess the action of metabotropic glutamate receptor (mGlu receptor) agonists on 4-aminopyridine (2 mM)-stimulated endogenous glutamate release. 4-Aminopyridine alone increased basal glutamate release by 6.89 +/- 0.74 nmol/mg. The mGlu receptor agonists L-2-amino-4-phosphonobutyric acid (L-AP4) (IC50 approximately 0.2 microM) and (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid (IC50 approximately 0.2 microM) inhibited 4-aminopyridine-stimulated release. The putative mGlu receptor antagonist (S)-alpha-methyl-L-AP4, which itself inhibited 4-aminopyridine-stimulated release (IC50 approximately 10 microM), did not inhibit the effects of the two agonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Aminobutyrates / pharmacology*
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Cycloleucine / analogs & derivatives*
  • Cycloleucine / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Male
  • Rats
  • Receptors, Metabotropic Glutamate / agonists*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism

Substances

  • 2-amino-2-methyl-4-phosphonobutyrate
  • Aminobutyrates
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Glutamic Acid
  • 4-Aminopyridine
  • 2-amino-4-phosphonobutyric acid