Modulation of NMDA receptor function by inhibition of d-amino acid oxidase in rodent brain

2011 ◽  
Vol 61 (5-6) ◽  
pp. 1001-1015 ◽  
Author(s):  
Christine A. Strick ◽  
Cheryl Li ◽  
Liam Scott ◽  
Brian Harvey ◽  
Mihály Hajós ◽  
...  
2016 ◽  
Vol 41 (1-2) ◽  
pp. 398-408 ◽  
Author(s):  
Henry Sershen ◽  
Audrey Hashim ◽  
David S. Dunlop ◽  
Raymond F. Suckow ◽  
Tom B. Cooper ◽  
...  

2007 ◽  
Vol 98 (1) ◽  
pp. 122-130 ◽  
Author(s):  
Eric C. Gustafson ◽  
Eric R. Stevens ◽  
Herman Wolosker ◽  
Robert F. Miller

We have combined electrophysiology and chemical separation and measurement techniques with capillary electrophoresis (CE) to evaluate the role of endogenous d-serine as an NMDA receptor (NMDAR) coagonist in the salamander retina. Electrophysiological experiments were carried out using whole cell recordings from retinal ganglion cells and extracellular recordings of the proximal negative response (PNR), while bath applying two d-serine degrading enzymes, including d-amino acid oxidase (DAAO) and d-serine deaminase (DsdA). The addition of either enzyme resulted in a significant and rapid decline in the light-evoked responses observed in ganglion cell and PNR recordings. The addition of exogenous d-serine in the presence of the enzymes restored the light-evoked responses to the control or supracontrol amplitudes. Heat-inactivated enzymes had no effect on the light responses and blocking NMDARs with AP7 eliminated the suppressive influence of the enzymes as well as the response enhancement normally associated with exogenous d-serine application. CE was used to separate amino acid racemates and to study the selectivity of DAAO and DsdA against d-serine and glycine. Both enzymes showed high selectivity for d-serine without significant effects on glycine. Our results strongly support the concept that endogenous d-serine plays an essential role as a coagonist for NMDARs, allowing them to contribute to the light-evoked responses of retinal ganglion cells. Furthermore under our experimental conditions, these coagonist sites are not saturated so that modulation of NMDAR sensitivity can be achieved with further modulaton of d-serine.


1996 ◽  
Vol 76 (06) ◽  
pp. 0993-0997
Author(s):  
Zhao-Yan Li ◽  
Xiao-Wei Wu ◽  
Tie-Fu Yu ◽  
Eric C-Y Lian

SummaryBy means of CM-Sephadex C-25, DEAE-Sephadex A-50, Sephadex G-200, and Sephadex G-75 chromatographies, a lupus anticoagulant like protein (LALP) from Agkistrodon halys brevicaudus was purified. On SDS-PAGE, the purified LALP had a molecular weight of 25,500 daltons under non-reducing condition and 15,000 daltons under reducing condition. The isoelectric point was pH 5.6. Its N terminal amino acid sequencing revealed a mixture of 2 sequences: DCP(P/S)(D/G)WSSYEGH(C/R)Q(Q/K). It was devoid of phospho-lipaseA, fibrino(geno)lytic, 5′-nucleotidase, L-amino acid oxidase, phosphomonoesterase, phosphodiesterase and thrombin-like activities, which were found in crude venom. In the presence of LALP, PT, aPTT, and dRVVT of human plasma were markedly prolonged and its effects were concentration-dependent but time-independent. The inhibitory effect of LALP on the plasma clotting time was enhanced by decreasing phospholipid concentration in TTI test. The individual clotting factor activity was not affected by LALP when higher dilutions of LALP-plasma mixture were used for assay. Russell’s viper venom time was shortened when high phospholipid confirmatory reagent was used. Therefore, the protein has lupus anticoagulant property.


1982 ◽  
Vol 48 (03) ◽  
pp. 277-282 ◽  
Author(s):  
I Nathan ◽  
A Dvilansky ◽  
T Yirmiyahu ◽  
M Aharon ◽  
A Livne

SummaryEchis colorata bites cause impairment of platelet aggregation and hemostatic disorders. The mechanism by which the snake venom inhibits platelet aggregation was studied. Upon fractionation, aggregation impairment activity and L-amino acid oxidase activity were similarly separated from the crude venom, unlike other venom enzymes. Preparations of L-amino acid oxidase from E.colorata and from Crotalus adamanteus replaced effectively the crude E.colorata venom in impairment of platelet aggregation. Furthermore, different treatments known to inhibit L-amino acid oxidase reduced in parallel the oxidase activity and the impairment potency of both the venom and the enzyme preparation. H2O2 mimicked characteristically the impairment effects of L-amino acid oxidase and the venom. Catalase completely abolished the impairment effects of the enzyme and the venom. It is concluded that hydrogen peroxide formed by the venom L-amino acid oxidase plays a role in affecting platelet aggregation and thus could contribute to the extended bleeding typical to persons bitten by E.colorata.


Author(s):  
Hong Wei ◽  
Zuyue Chen ◽  
Ari Koivisto ◽  
Antti Pertovaara

Abstract Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, σ1 and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (σ1 receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the σ1 and NMDA receptors, and DAAO.


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