Presynaptic group I and II metabotropic glutamate receptors oppositely modulate striatal acetylcholine release.
The effect of metabotropic glutamate receptor agonists and antagonists on KCl (20 mm)-induced endogenous acetylcholine release from rat striatal synaptosomes was investigated. The group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG), 1-1000 nm, potentiated in a concentration-dependent way the KCl-induced acetylcholine release, reaching maximal efficacy at 100 nm (+93 +/- 14%). The effect of DHPG (10 nm) was counteracted by coapplication of (7-hydroximino)cyclopropan-b-chromen-1a-carboxylate (CPCCOEt), 10 microm, a metabotropic glutamate receptor type one selective antagonist, and 2-methyl-6-(phenylethynyl)pyridine (MPEP), 10 microm, a metabotropic glutamate receptor type five 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)glycine (DCG-IV), 1-1000 nm, inhibited in a concentration-dependent way the KCl-induced acetylcholine release displaying maximal efficacy at 300 nm (-32 +/- 2%). The effect of DCG-IV 300 nm was counteracted by the group II selective antagonist (2S)-alpha-ethylglutamic acid (EGLU), 300 microm. The group III agonist L-amino-4-phosphonobutyric acid (L-AP4) failed to alter the KCl-induced acetycholine release up to 300 microm. We conclude that metabotropic glutamate receptors belonging to group I and II are located on the axon terminals of striatal cholinergic interneurons, their activation resulting in facilitation and inhibition, respectively, of acetylcholine release.
Marti
M
M
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
Paganini
F
F
Stocchi
S
S
Bianchi
C
C
Beani
L
L
Morari
M
M
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C104077:metabotropic glutamate receptor type 1; D000109:Acetylcholine