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Group I and II metabotropic glutamate receptors alter brain cortical metabolic and glutamate/glutamine cycle activity: a 13 C NMR spectroscopy and metabolomic study
Author(s) -
Rae Caroline,
ElHajj Moussa Charbel,
Griffin Julian L.,
Bubb William A.,
Wallis Trent,
Balcar Vladimir J.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02880.x
Subject(s) - metabotropic glutamate receptor , glutamine , glutamate receptor , chemistry , metabotropic receptor , metabolism , biochemistry , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 2 , biology , amino acid , receptor
Metabotropic glutamate receptors (mGluR) modulate neuronal function. Here, we tested the effect on metabolism of a range of Group I and II mGluR ligands in Guinea pig brain cortical tissue slices, applying 13 C NMR spectroscopy and metabolomic analysis using multivariate statistics. The effects of Group I agonists ( S )‐3,5‐dihydroxyphenylglycine (DHPG) and ( RS )‐2‐chloro‐5‐hydroxyphenylglycine (CHPG) depended upon concentration and were mostly stimulatory, increasing both net metabolic flux through the Krebs cycle and glutamate/glutamine cycle activity. Only the higher (50 µ m ) concentrations of CHPG had the opposite effect. The Group I antagonist ( RS )‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA), consistent with its neuroprotective role, caused significant decreases in metabolism. With principal components analysis of the metabolic profiles generated by these ligands, the effects could be separated by two principal components. Agonists at Group II mGluR [(2 S ,2′ R ,3′ R )‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG IV) and 2 R ,4 R ‐4‐aminopyrrolidine‐2,4‐dicarboxylate (APDC)] generally stimulated metabolism, including glutamate/glutamine cycling, although this varied with concentration. The antagonist (2 S )‐α‐ethylglutamic acid (EGLU) stimulated astrocyte metabolism with minimal impact on glutamate/glutamine cycling. ( RS )‐1‐Aminophosphoindan‐1‐carboxylic acid (APICA) decreased metabolism at 5 µ m but had a stimulatory effect at 50 µ m . All ligand effects were separated from control and from each other using two principal components. The ramifications of these findings are discussed.