Peripheral glutamate receptors: Molecular biology and role in taste sensation

Glutamate is the most widespread excitatory neurotransmitter in the mammalian brain. Two classes of glutamate receptor have been cloned, the ionotropic (ligand-gated ion channels) and the metabotropic (G protein-coupled receptors). Three subclasses of ionotropic glutamate receptors are known; they are named after selective agonists, i.e., alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. Fifteen functional subunits assemble together in heteromultimeric complexes to form these receptors as follows: GluR1-GluR4 for AMPA; GluR5-GluR7 and KA1-KA2 for kainate; and NR1, NR2A-NR2D and NR3 for NMDA receptors. Within a subclass, the subunit composition strongly influences the pharmacologic and biophysical properties of the receptors. The metabotropic glutamate receptors fall into the following three groups, each containing two or more individual receptor proteins: group I (mGluR1, mGluR5), group II (mGluR2, mGluR3), and group III (mGluR4, mGluR6, mGluR7 and mGluR8). In contrast to the ionotropic receptors, the metabotropic glutamate receptors appear to act as monomers or homodimers rather than heteromers. Messenger RNAs encoding several ionotropic subunits and a mGluR4-like receptor have been identified in taste buds. Although controversial, the evidence is consistent with an NMDA receptor sewing as a primary taste transducer for monosodium glutamate (MSG), and a metabotropic glutamate receptor modulating the flavor-enhancing effect of MSG. Thus the neurotransmitter glutamate is intimately involved in the central processing of taste information.