Table 3

Endogenous extracellular voltage-independent modulation of NMDA receptor function

ModulatorEffectEC50Maximal Effect3-a
DynorphinInhibition0.3 μM3-b  100%Chen et al., 1995 a, b; Brauneis et al., 1996; Zhang et al., 1997; Chen and Huang, 1998
Osmotic pressureInhibition  75% Paoletti and Ascher, 1994
Oxidizing agentsInhibition  70%3-c Aizenman et al., 1989, 1990, 1992; Tang and Aizenman, 1993 a,b
ProtonsInhibition50–200 nM3-d  100%reviewed by Traynelis, 1998
Sulfated steroidsInhibition150 μM3-e  100% Park-Chung et al., 1994, 1997
ZincInhibition0.2–2 μM3-g 100–80% Smart et al., 1994; Williams, 1996; Chen et al., 1997; Paoletti et al., 1997; Traynelis et al., 1998
Arachidonic acidPotentiation10 μM2-fold Miller et al., 1992; Petrou et al., 1993; Horimoto et al., 1996; Mishikawa et al., 1994; Tabuchi et al., 1997
PACAP3-g Potentiation<1 μM3-foldLiu and Madsen, 1997; Wu and Dunn, 1997
Polyamines, histaminePotentiation100 μM3-h 2-fold Johnson, 1996; Williams, 1997a,b
Reducing agentsPotentiation3-foldAizenman et al., 1989, 1990, 1992; Tang and Aizenman, 1993 a,b
Sulfated steroidsPotentiation12 μM3-i 2.5-fold Park-Chung et al., 1997
  • 3-a Other exogenous modulators have been described: ethanol (Peoples and Weight, 1995, 1998; Masood et al., 1994; Peoples et al., 1997); ifenprodil (Legendre and Westbrook, 1991; Kew et al., 1996; Mott et al., 1998), and conanotokins (Zhou et al., 1996). Maximal inhibition (100% is full inhibition) or x-fold potentiation.

  • 3-b Dynorphin A 1-32.

  • 3-c The response of fully reduced receptors (e.g., dithiothreitol treated) is decreased by 70% by oxidizing agents.

  • 3-d Proton inhibition depends on subunit composition.

  • 3-e 3β-hydroxy-5β-pregnan-20-one sulfate.

  • 3-f NR2A-containing receptors are much more sensitive to extracellular Zn2+ than receptors containing other subunits; NR2C and NR2D are much less sensitive to Zn2+.

  • 3-g Pituitary adenylyl cyclase-activating peptide.

  • 3-h Spermine.

  • 3-i Pregnanalone sulfate.