Polyamine-modulatory site

Just as does the GABA-benzodiazepine receptor complex discussed in Chapter 8 (see Figs. 8-18 to 8—20), the NMDA glutamate—calcium channel complex also has multiple receptors surrounding the ion channel, which act in concert as allosteric modulators (Fig. 10—24). One modulatory site is for the neurotransmitter glycine another is for polyamines, and yet another is for zinc (Fig. 10—24). The magnesium ion can block the calcium channel at yet another modulatory site, which is presumably inside the ion channel or closely related to it. Another inhibitory modulatory site,... 

A polyamine-binding site is in the NMDA receptor complex (Singh et al., 1990 Ransom and Stec, 1988). Like the glycine-binding site, the polyamine modulatory... 

NMDA receptors ( Figure 1.3-2) are the most complex of the ionotropic receptors. In addition to the recognition site for glutamate, NMDA receptors contain several allosteric modulatory sites, including (1) a site for the endogenous brain amino acids glycine and D-serine, (2) a polyamine-sensitive site, and (3) a redox site that is sensitive to glutathione (see Chapter 2.5 this volume). All sites act primarily to facilitate activity at the receptor. 

Figure 14.8. Sites of action of endogenous ligands and drugs that modulate the action of excitatory amino acids on the NMDA receptor. Recent evidence shows that glutamate (Glut) and possibly other excitatory amino acids released from presynaptic terminals activate the NMDA receptor site on postsynaptic membranes, resulting in the opening of the Na+/Ca++ channels. Glycine acts on a strychnine-insensitive receptor while polyamines (e.g. spermine and spermidine) also have a modulatory role. Conversely Zn++ and Mg++ and drugs like phencyclidine (PCP) block the ion channel by acting at various sites on the NMDA receptor complex or...

NMDA-Glu-Rs are 4 to 5 subunit complexes of NR1, NR2 (A-D) and NR3 subunits with sites for various modulatory ligands including NMDA, Gly (at a strychnine-insensitive site) and ion channel blocking entities such as polyamines, Zn2+ and Mg2+ (Table 3.3). 

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