Glycine transport accounts for the differential role of glycine vs. D-serine at NMDA receptor coagonist sites in the salamander retina.

In this study, we demonstrate that d-serine interacts with N-methyl-d-aspartate receptor (NMDAR) coagonist sites of retinal ganglion cells of the tiger salamander retina by showing that exogenous d-serine overcomes the competitive antagonism of 7-chlorokynurenic acid for this site. Additionally, we show that exogenous d-serine was more than 30 times as effective at potentiating NMDAR currents compared with glycine. We thus examined the importance of glycine transport through the application of selective antagonists of the GlyT1 (NFPS) and GlyT2 (ALX-5670) transport systems, while simultaneously evaluating the degree of occupancy of the NMDAR coagonist binding sites.

Light-evoked NMDA receptor-mediated currents are reduced by blocking D-serine synthesis in the salamander retina.

Experiments were carried out in the retina of the tiger salamander (Ambystoma tigrinum) to evaluate the importance of D-serine synthesis on light-evoked N-methyl D-aspartate (NMDA) receptor-mediated components of ganglion cells and contributions to the proximal negative field potential. We blocked the synthesis of D-serine through brief exposures of the retina to phenazine ethosulfate and validated the changes in the tissue levels of D-serine using capillary electrophoresis methods to separate and measure the amino acid enantiomers. Ten minute exposures to phenazine ethosulfate decreased D-serine levels in the retina by about 50% and significantly reduced the NMDA receptor contribution to light responses of the inner retina.

Endogenous D-serine contributes to NMDA-receptor-mediated light-evoked responses in the vertebrate retina.

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.

D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors.

d-serine has been proposed as an endogenous modulator of N-methyl-d-aspartate (NMDA) receptors in many brain regions, but its presence and function in the vertebrate retina have not been characterized. We have detected d-serine and its synthesizing enzyme, serine racemase, in the retinas of several vertebrate species, including salamanders, rats, and mice and have localized both constituents to Müller cells and astrocytes, the two major glial cell types in the retina. Physiological studies in rats and salamanders demonstrated that, in retinal ganglion cells, d-serine can enhance excitatory currents elicited by the application of NMDA, as well as the NMDA receptor component of light-evoked synaptic responses.

Effect of ondansetron, a 5-HT3 receptor antagonist, on the dynamic association between bulimic behaviors and pain thresholds.

Thresholds for detection of both pressure and thermal pain are elevated in patients with bulimia nervosa. The present study was aimed at determining (1) if pressure pain detection thresholds (PDT) varied dynamically with the primary disease symptoms of binge eating and vomiting and (2) if the elevation in PDT was effected by treatment with ondansetron (ONDAN), a 5-HT3 receptor antagonist. PDT was defined as the mean of the minimal amount of pressure (measured in g) perceived as painful when exerted by a 1 mm2 blunted point onto the center of the ventral surface of the ungual phalanx of digits 2-5 of the non-dominant hand.