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.
East
S J
SJ
Division of Neuroscience, School of Biological Sciences, Manchester University, UK.
Hill
M P
MP
Brotchie
J M
JM
D015761:4-Aminopyridine / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
C089836:2-amino-2-methyl-4-phosphonobutyrate; D000613:Aminobutyrates; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D015761:4-Aminopyridine; C012729:2-amino-4-phosphonobutyric acid