Metabotropic glutamate receptor: Its ligands and function in the olfactory system

Abstract

The metabotropic glutamate receptors (mGluRs) consist of at least eight different subtypes. However, the lack of specific ligands for this class of receptors limited the characterization of their roles. In this study, a series of glutamate derivatives was systematically tested for agonist and antagonist activities for the mGluR subtypes, individually expressed in cell lines. Among various compounds tested, (2S, 1'R, 2'R, 3'R)-2-(2,3- dicarboxycyclopropyl)glycine (DCG-IV) was found to be an effective agonist for mGluR2 and α-methyl-4-carboxyphenylglycine (αM4CPG) was found to be an antagonist for both mGluR1 and mGluR2. Using DCG-IV, I showed that mGluR2 mediates presynaptic inhibition of GABA release from granule cells at the dendrodendritic synapse of the accessory olfactory bulb (AOB). This mechanism was considered to relieve a mitral cell from GABAergic inhibition and, furthermore, to be involved in lateral inhibition of surrounding mitral cells and thus enhancing the signal/noise ratio of olfactory sensation. I also show that an activation of mGluR2 in AOB by infusion of DCG-IV induces olfactory memory, which can mimic the pregnancy block phenomenon of female mice. This is the first report of a role of specific subtype of mGluR in the central nervous system.