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

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.