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

• Published in: European journal of pharmacology Vol. 277; no. 1; pp. 117 - 121
• Main Authors: East, Stephen J., Hill, Michael P., Brotchie, Jonathan M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13-04-1995; Elsevier
• Subjects: 4-Aminopyridine - pharmacology; Aminobutyrates - pharmacology; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Cycloleucine - analogs & derivatives; Cycloleucine - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Glutamate release; Glutamic Acid - metabolism; Male; Metabotropic glutamate receptor; Parkinson's disease; Presynaptic; Rats; Receptors, Metabotropic Glutamate - agonists; Striatum; Synaptosome; Synaptosomes - drug effects; Synaptosomes - metabolism; Vertebrates: nervous system and sense organs; Striatum; Glutamate release; Synaptosome; Parkinson's disease; Metabotropic glutamate receptor; Presynaptic; Nervous system diseases; Agonist; Rat; Rodentia; Parkinson disease; Corpus striatum; Glutamate receptor; Glutamate; Antiparkinson agent; In vitro; Biological activity; Cerebral disorder; Vertebrata; Mammalia; Metabotropic receptor; Animal; Central nervous system disease; Degenerative disease; Mechanism of action; Extrapyramidal syndrome
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00119-6

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) (IC
50 ≈ 0.2 μM) and (1
S,3
S)-1-amino-cyclopentane-3,3-dicarboxylic acid (IC
50 ≈ 0.2 μM) inhibited 4-aminopyridine-stimulated release. The putative mGlu receptor antagonist (
S)-α-methyl-
l-AP4, which itself inhibited 4-aminopyridine-stimulated release (IC
50 ≈ 10 μM), did not inhibit the effects of the two agonists.