[Functional coupling between metabotropic glutamate receptors and G proteins in rat cerebral cortex].
Metabotropic glutamate receptors (mGluRs) are widely distributed in mammalian brain, and are classified into three groups (Group I-III) according to mode of action: by I) homology of amino acid sequence, II) ligand selectivity, and III) signal transduction pathway. The mGluR-mediated signaling cascade is mainly investigated with the use of receptor-expressed non-neuronal cells; and thus, signaling mechanism in the central nervous systems remains to be elucidated. The aim of this study was to elucidate the manner of mGluR-G protein coupling in rat brain by measuring the activities of the high-affinity, low-KM GTPases in G alpha proteins. The selective Group II mGluR agonists, i.e., 2-(2,3-dicarboxycyclopropyl)glycine and (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate, elevated GTP hydrolysis in a concentration-dependent and saturable manner. On the other hand, the activation of high-affinity GTPase by the selective Group I mGluR agonist, (S)-3-hydroxyphenylglycine, or the selective Group III agonist, L-2-amino-4-phosphonobutylate, was hardly detected. These results indicated that the fashion of mGluR-G protein coupling varies among the mGluR subgroups. It is also suggested that high-affinity GTPase assay is useful for the investigation of mGluR-mediated signal transduction in the brain.
Nishi
N
N
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003521:Cyclopropanes / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000032:analysis; D019204:GTP-Binding Proteins / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D003521:Cyclopropanes; D018094:Receptors, Metabotropic Glutamate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; C023010:4-hydroxyphenylglycine; D011392:Proline; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D005998:Glycine