NMDA receptors function

Aizenman E, Hartnett KA, Reynolds IJ Oxygen free radicals regulate NMDA receptor function via a redox modulatory site. Neuron 5 841—846, 1990... 

Kohr G (2006) NMDA receptor function subunit composition versus spatial distribution. Cell... 

Studies reveal that a homozygous GlyT-1 (-/-) knockout in mice is neonatally lethal. However heterozygous GlyT-1 (+/-) mice survive to adulthood and display enhanced NMDA receptor function in the hippocampus, better memory retention, and no disruption in sensory gating when dosed with amphetamine [15]. 

Anandamide has dual effects on NMDA receptor function. It reduces NMDA Ca2-i- currents, which is mediated by cannabinoid receptors and G-protein mechanisms (Hampson et al. 1998). However, anandamide potentiates NMDA currents due to a direct effect on the NMDA receptor itself. THC did not have the same effect. So anandamide appears to have at least one other CNS effect that is not through the cannabinoid receptors. THC also reduces AMPA/kainate activity, which is mediated by CBl receptors (Shen and Thayer 1999) (table 10.5). THC may in-... 

D-cycloserine and (-l-R)-HA-966 are partial agonists at the glycincB site with different levels of intrinsic activity (Karcz-Kubicha et al. 1997). Although these systemically active partial agonists do not induce receptor desensitization they have favourable therapeutic profiles in some in vivo models (Lanthorn 1994 see Danysz and Parsons 1998). This may, in part, be due to their own intrinsic activity as agonists at the glycines site, which would serve to preserve a certain level of NMDA receptor function even at very high concentrations (Danysz and Parsons 1998). 

Abnormalities of the glutamate system have also been documented in neuropsychiatric disorders. For example, compounds such as PCP and ketamine, which block the NMDA receptor, can induce psychotic symptoms. By contrast, compounds such as d-cycloserine or glycine, which increase NMDA receptor function via the glycine binding site, can decrease psychotic and/or negative symptoms in schizophrenia (Farber et ah, 1999 Goff et ah, 1999, Fleresco-Levy et ah, 1999). 

We demonstrated for the first time that crocin selectively antagonizes the inhibitory effect of ethanol on NMDA-receptor-mediated responses in hippocampal neurons. This action of crocin may underlie the antagonism against ethanol-induced memory impairment. Crocin should be useful as a new pharmacological tool for studying the mechanism of ethanol inhibition of NMDA receptor functions. 

Unfortunately a global knock-out of NR1 subunits (i.e. a total deficit of NMDA receptor functionality) produces non-viable offspring which die perinatally within hours (Forrest et al., 1994 Li et al., 1994). The non-viable offspring suffer from respiratory distress, cyanosis, and severe ataxia. In addition, due to neurophysiological abnormalities they do not develop any suckling reflex. 

Calmodulin (CaM), a Ca2+-binding protein, binds directly to the NR1 subunit of the NMDA receptor in a Ca2+-dependent manner. CaM binding occurs at two distinct sites in the COOH -terminal region of NR1 molecule. One CaM binding site is contained within the spliced Cl exon cassette, whereas the other is located in a region common to all NR1 splice variants (Ehlers et al., 1996). Collective evidence suggests that NMDA receptor function can be modulated by CaM binding to the NR1 subunit and this process may be related to activity-dependent feedback inhibition and Ca2+-dependent inactivation of NMDA receptors. 

Okabe S., Vicario-Abejon C., Segal M., and McKay R. D. (1998). Survival and synaptogenesis of hippocampal neurons without NMDA receptor function in culture. Eur. J. Neurosci. 10 2192-2198. 

Fan M. M. and Raymond L. A. (2007). N-Methyl-d-aspartate (NMDA) receptor function and exci-totoxicity in Huntington s disease. Prog. Neurobiol. 81 272-293. 

Gingrich, M.B., et al. 2000. Potentiation of NMDA receptor function by the serine protese thrombin. J Neurosci 20 4582. 

Pittaluga A, Bonfanti A, Raiteri M (2000) Somatostatin potentiates NMDA receptor function via activation of InsP3 receptors and PKC leading to removal of the Mg2+ block without depolarization. Br J Pharmacol 130 557-66... 

Risso F, Grilli M, Parodi M et al (2004) Nicotine exerts a permissive role on NMDA receptor function in hippocampal noradrenergic terminals. Neuropharmacology 47 65-71 Rodrigues RJ, Alfaro TM, Rebola N et al (2005) Co-localization and functional interaction between adenosine A2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J Neurochem 92 433 41... 

Experimental studies have also suggested that alcohol may reduce N-methyl-D-aspartate (NMDA) receptor function following acute administration, and following withdrawal of alcohol the functioning of these receptors is enhanced. 

NMDA receptor function and emotional reactivity changes in rat offspring. Cereb. Cortex doi 10.1093/cercor/bhi076. 

NMDA Receptor Function, Neuroplasticity, and the Pathophysiology of Schizophrenia Joseph T. Coyle and Guochuan Tsai... 

Gabernet L, Pauly-Evers M, Schwerdel C, Lentz M, Bluethmann H, et al. 2005. Enhancement of the NMDA receptor function by reduction of glycine transporter-1 expression. Neurosci Lett 373 79-84. 

Malhotra AK, Pinals DA, Weingartner H, Sirocco K, Missar CD, et al. 1996. NMDA receptor function and human cognition The effects of ketamine in healthy volunteers. Neuropsychopharmacology 14 301-307. 

Coyle JT, Tsai G. 2004. NMDA receptor function, neuroplasticity, and the pathophysiology of schizophrenia. Int Rev Neurobiol 59 491-515. 

Lee FJ, Xue S, Pei L, Vukusic B, Chery N, Wang Y, Wang YT, Niznik HB, Yu XM, Liu F (2002a) Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell 777 219-230. 

A. Breier. NMDA Receptor Function and Human Cognition the Effects of Ketamine in Healthy Volunteers. Neuropsychopharmacology 14 (5) (1996) 301-307. 

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