High extracellular glycine does not potentiate N-methyl-d-aspartate-evoked depolarization in vivo

Obrenovitch, Tihomir P.; Hardy, Aidan M.; Urenjak, Jutta

doi:10.1016/s0006-8993(96)01197-3

Cited by 23 publications

(11 citation statements)

References 48 publications

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“…These data seem to support the view that the effective Gly concentration in the synaptic cleft could be much lower (nM range), due to the action of Gly transporters strategically placed around the synapse (Javitt and Heresco-Levy 2000). However, some controversy still exists as to the nature and role of the interaction of Gly and the NMDAr in vivo, with multiple studies showing the lack of modulatory effects following the application of Gly site agonists (Long et al 2007;Meur et al 2007;Obrenovitch et al 1997). Such discrepant results have led some authors to propose that the degree of NMDA Gly site saturation might be region-dependent (Li and Han 2007;Ballard et al 2002).…”

Section: Introductionsupporting

confidence: 58%

Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat

et al. 2008

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Section: Introductionsupporting

confidence: 58%

Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat

et al. 2008

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“…The reason for this difference is still unclear but may be related to endogenous NMDA receptor-like proteins in these cells or different expression mechanisms. There is still some debate whether the glycineB site is saturated in vivo (Peeters et al, 1992;Matsui et al, 1995;Wood et al, 1995;Fedele et al, 1997;Obrenovitch et al, 1997) but it seems likely that the degree of NMDA receptor activation varies depending on regional differences in receptor subtype expression and local glycine or Dserine concentrations. Moreover, glycine concentrations at NMDA receptors can be finely modulated by local expression of specific glycine transporters (Virgo et al, 1995, Malandro andKilberg, 1996;Supplisson and Bergman, 1996;Javitt et al, 1997).…”

mentioning

confidence: 99%

Modulation of NMDA receptors by glycine ? introduction to some basic aspects and recent developments

et al. 1998

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Glycine is a co-agonist at NMDA receptors and it's presence is a prerequisite for channel activation by glutamate or NMDA. Physiological concentrations reduce one form of NMDA receptor-desensitization. Interactions between the glycineB site and other domains of the NMDA receptor are complex and include the glutamate, Mg2+ and polyamines sites. Glycine shows different affinities at various NMDA receptor subtypes probably via to allosteric interactions between NMDA2 subunits and the glycine recognition site on the NMDAR1 subunit. There is still some debate whether the glycineB site is saturated in vivo but it seems likely that this depends on regional differences in receptor subtype expression, local glycine or D-serine concentrations and the expression of specific glycine transporters. GlycineB antagonists and partial agonists have been reported to have good therapeutic indices as neuroprotective agents against focal ischaemia and trauma, anti-epileptics, anxiolytics, anti-psychotomimetics and in models of chronic pain. They clearly lack two potentially serious side effects classically associated with NMDA receptor blockade, namely neurodegenerative changes in the cingulate/retrosplenial cortex and psychotomimetic-like effects. This improved therapeutic profile may be partially due to the ability of full glycineB antagonists to reveal glycine-sensitive desensitization and possibly also via functional and/or regional NMDA receptor subtype selectivity.

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“…However, it is likely that excitotoxicity is involved at least in part in the neuropathology of this disorder since Gly is a co-agonist of NMDA receptors (McNamara and Dingledine, 1990;Patel et al, 1990;Hara et al, 1993;Kure et al, 1997;Katsuki et al, 2007;Kono et al, 2007;Kikuchi et al, 2008). On the other hand, considering that normal Gly values in human body fluids are sufficiently high to saturate the binding site for Gly on the NMDA-type glutamate receptors, it is feasible that higher concentrations of Gly may not cause overstimulation of these receptors (Obrenovitcha et al, 1997). Thus, other mechanisms may underlie brain damage in NKH.…”

Section: Discussionmentioning

confidence: 99%

Glycine intrastriatal administration induces lipid and protein oxidative damage and alters the enzymatic antioxidant defenses in rat brain

et al. 2011

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The data shows that Gly in vivo administration causes lipid peroxidation, probably secondary to NMDA stimulation, induces protein oxidation and modulates the activities of important antioxidant enzymes in the striatum. In case these findings can be extrapolated to the human NKH, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this neurometabolic disease.

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High extracellular glycine does not potentiate N-methyl-d-aspartate-evoked depolarization in vivo

Cited by 23 publications

References 48 publications

Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat

Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat

Modulation of NMDA receptors by glycine ? introduction to some basic aspects and recent developments

Glycine intrastriatal administration induces lipid and protein oxidative damage and alters the enzymatic antioxidant defenses in rat brain

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