Abstract:
:Group III metabotropic glutamate receptors (mGluR4, 6, 7, 8) are negatively coupled to adenylate cyclase and, when activated presynaptically, decrease the release of glutamate and GABA. We have used intracerebroventricular injections of agonists and antagonists believed to act selectively on these receptors to study the pro- or anti-convulsant effects of mGluR III activation in nonepileptic (Swiss-Webster) and epileptic (DBA/2) mice. In both mouse strains the prototypic agonists L-2-amino-4-phosphonobutanoate (LAP4) and L-serine-O-phosphate are proconvulsant. The supposed antagonists (S)-2-methyl-2-amino-4-phosphonobutanoate (MAP4) and (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG), have a predominantly proconvulsant effect. (S)-alpha-methyl-3-carboxyphenylalanine, which is a potent and selective antagonist for LAP4 in the cortex, is anticonvulsant in DBA/2 mice and decreases the convulsant effect of N-methyl-D-aspartate, 3,5-dihydroxyphenylglycine, LAP4 and MPPG in Swiss-Webster mice. These data suggest that reduced inhibitory transmission may be more significant than reduced synaptic release of glutamate following group III mGluR activation.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Ghauri M,Chapman AG,Meldrum BSdoi
10.1097/00001756-199606170-00005subject
Has Abstractpub_date
1996-06-17 00:00:00pages
1469-74issue
9eissn
0959-4965issn
1473-558Xjournal_volume
7pub_type
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