NMDA receptor activation

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites,... 

Dumuis, A, Sebben, M, Haynes, L, Pin, JP and Bockaert, J (1988) NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336 68-70. 

In common with neuropathy, NMDA receptor activation occurs after inflammation but here opioid actions are enhanced since CCK levels decrease. Thus, this augmented opioid actions may counter the increased excitability without the need for large increase in doses of opioid. 

SMALL GTP-BINDING PROTEINS (GTPases) MEDIATE CHANGES IN GENE EXPRESSION UPON NMDA RECEPTOR ACTIVATION 285... 

In vitro studies on excitotoxicity suggest that while both NMDA and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate (KA) receptors can mediate excitotoxicity (see Ch. 15), these classes of glutamate receptors do not do so equally. Experiments with cortical or hippocampal cell cultures suggest that much of the neuronal death associated with brief, intense glutamate exposure is mediated by NMDA receptor activation, probably because this can induce lethal amounts of Ca2+ influx more rapidly than can AMPA/KA receptor stimulation. 

However, overactivation of AMPA or KA receptors can also lead to intracellular Ca2+ overload and neurodegeneration. This maybe especially true under conditions where NMDA-receptor activity is reduced by extracellular acidity or a buildup of extracellular Zn2+ [ 12]. It is also true with respect to specific neuronal subpopulations that express AMPA-sensitive Ca2+ channels (see Ch. 15). G-protein-linked metabotropic glutamate receptors (mGluRs) appear not to mediate excitotoxicity directly but, rather, to modify the degree of excitotoxic injury. 

Reports that AA is released primarily by G-protein-mediated PLA2 activation remain to be confirmed [84, 85]. In addition, modulation of PLA2 by Ca2+ and protein kinase needs to be better defined. It is clear that NMDA receptor activation promotes the release of AA [86], and that a variety of eicosanoids are then generated (Fig 33-2,33-3). The modulatory events that channel AA towards specific eicosanoids are not understood. The endocannabinoid family of lipid messengers will remain an active focus of interest because of the growing evidence of their actions in synaptic function, learning, memory, and other forms of behavior [56,87]. 

Kainate receptors have recently been implicated in the induction of EIP in the mossy fibers (49,85). Unlike EIP in the area CA1, induction of mossy-fiber EIP is independent of NMDA-receptor activation and involves presynaptic mechanisms (105). Synaptic activation of the facilitatory presynaptic receptor can account for the role of KA receptors in the induction of mossy-fiber LIP by maintaining a high level of release during high-frequency transmission (77). Furthermore, following induction of LTP, the presynaptic kainate receptor-mediated facilitation of synaptic transmission is lost, suggesting that the mechanism by which presynaptic kainate receptors facilitate... 

Reynolds IJ, Hastings TG (1995) Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation. J. Neurosci. 15 ... 

Said, S. L, Pakbaz, H., Berisha, H. L, and Raza, S. (2000). NMDA receptor activation Critical role in antioxidant tissue injury. Free Radio. Bio. Med. 28,1300-1302. 

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