Receptor glutamate superfamily

The NMDA, AMPA, and kainate subtypes of glutamate receptors are probably all linked to an ion channel. The metabotropic glutamate receptor subtype, however, belongs to the G protein—linked superfamily of receptors. The specific functioning of the various subtypes of glutamate receptors is the focus of intense debate. The actions at NMDA receptors will be emphasized here in our discussions on excitotoxicity. 

Fig. 1 Structures of subunits (top) and subunit oligomerization (bottom) in ligand-gated ion channels. (a) P2X receptor family, (b) Ionotropic glutamate receptor family, (c) TRPV channel family, (d) Cys-loop superfamily comprising nAChRs, 5-HT3,GABAa, and glycine receptors.

As mentioned above, members of the superfamily of ionotropic glutamate receptors are tetramers composed out of a repertoire of at least 18 subunits. They can be categorized into three families N-methyl-D-aspartate (NMDA) receptors, a-amino-3-hydroxy-5-methyl-4-isoxazolepropioinic acid (AMPA) receptors, and kainate receptors, the two latter forming the group of non-NMDA receptors. While NMDA receptors are composed of NR1, -2 (A, B, C, and D), and -3 (A and B)... 

The insect GABA receptor-chloride ionophore complex is found in the CNS and also at peripheral neuromuscular sites. GABA receptors belong to a superfamily of ligand-gated ion channels known as Cys-loop receptors that include nicotinic acetylcholine receptors and glutamate-gated chloride channels (Lester, 2004). Cys-loop receptors are so named because... 

PR, AR, GR, MR), thyroid hormone (TRa and j8), and retinoid (RARot, jS, and 7, and RXRa) receptor superfamily of nuclear transcriptional factors (207-210), multiple members of the interleukin cytokine receptor family (211), and subtypes of the glutamate (212) and adenosine (213)receptor families. The importance of access to human cloned receptors continues to be underscored as receptor binding plays an increasingly critical role in modern drug discovery (214). 

These characteristics are shared with subunits that form other ion channels/receptors and thus define a receptor superfamily, usually referred to as the nicotinic family. All members in this superfamily function as either cation- or anion-selective channels, thereby mediating fast excitatory or inhibitory synaptic transmission. In mammalian cells, the cation-selective members include nicotinic and 5HTg receptors, whereas the anion-selective members include GABA, GAB Ac, and glycine receptors. Anion-selective channels in this family are also found in invertebrates these channels are gated by glutamate, 5-HT, histidine, and acetylcholine (1). 

Figure 16.9 Cartoon illustrating the hypothetical transmembrane topology (left side) and subunit stoichiometry (right side) of the three basic ligand-gated channel superfamilies (1) cys-loop channels (2) glutamate receptor channels and (3) ATP-gated/P2X purinergic receptor channels. The numbers above the arrows refer to the number of subunits that make up the channel pore. The hypothetical ligand-binding sides are indicated in red.

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