Exaggerated responses to chronic nociceptive stimuli and enhancement of N-methyl-D-aspartate receptor-mediated synaptic transmission in mutant mice lacking D-amino-acid oxidase.
Formalin-induced nociceptive behaviors and N-methyl-D-aspartate (NMDA) subtype glutamate receptor-mediated excitatory synaptic transmission were analyzed in mutant mice lacking D-amino-acid oxidase, which catalyzes the oxidative deamination of D-amino acids. The second phase of the formalin-induced licking response, a part of which is known to be mediated by NMDA receptors in the spinal cord, was significantly augmented in mutant mice. NMDA receptor-mediated excitatory postsynaptic currents recorded from spinal cord dorsal horn neurons by tight-seal whole-cell methods were significantly potentiated in mutant mice. The present observations provide another line of evidence that D-serine functions as an endogenous coagonist at the glycine site of NMDA receptors, and raise the possibility that D-amino-acid oxidase exerts a neuromodulatory function by controlling the concentration of D-serine in the central nervous system.
Wake
K
K
Department of Anesthesiology, Dokkyo University School of Medicine, Mibu, 321-0293, Tochigi, Japan.
Yamazaki
H
H
Hanzawa
S
S
Konno
R
R
Sakio
H
H
Niwa
A
A
Hori
Y
Y
D000818:Animals; D003605:D-Amino-Acid Oxidase / Q000172:deficiency*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D010147:Pain Measurement / Q000379:methods; D020671:Posterior Horn Cells / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D003605:D-Amino-Acid Oxidase