Presynaptic group I and II metabotropic glutamate receptors oppositely modulate striatal acetylcholine release

The effect of metabotropic glutamate receptor agonists and antagonists on K Cl (20 mM)-induced endogenous acetylcholine release from rat striatal synap tosomes was investigated. The group I agonist (S)-3,5-dihydroxyphenylglycin e (DHPG), 1-1000 nm, potentiated in a concentration-dependent way the KCI-i nduced acetylcholine release, reaching maximal efficacy at 100 nM (+93 +/- 14%). The effect of DHPG (10 nm) was counteracted by coapplication of (7-hy droximino)cyclopropan-b-chromen-1a-carboxylate (CPCCOEt), 10 muM, a metabot ropic glutamate receptor type one selective antagonist, and 2-methyl-6(phen ylethynyl)pyridine (MPEP), 10 muM, a metabotropic glutamate receptor type f ive selective antagonist, but not by application of either antagonist alone . The group II agonist (2S, 1'R, 2'R, 3'R)-2-(2,3-dicarboxycyclopropyl)glyc ine (DCG-IV), 1-1000 nm, inhibited in a concentration-dependent way the KCI -induced acetylcholine release displaying maximal efficacy at 300 nm (-32 /- 2%). The effect of DCG-IV 300 nm was counteracted by the group II select ive antagonist (2S)-alpha -ethylglutamic acid (EGLU), 300 muM. The group II I agonist L-amino-4-phosphonobutyric acid (L-AP4) failed to alter the KCI-i nduced acetycholine release up to 300 Km. We conclude that metabotropic glu tamate receptors belonging to group I and II are located on the axon termin als of striatal cholinergic interneurons, their activation resulting in fac ilitation and inhibition, respectively, of acetylcholine release.