The co-agonist concept: is the NMDA-associated glycine receptor saturated in vivo?
Our current knowledge of the structure and function of NMDA receptors is expanding at a rapid pace; however, advances regarding regulation of the supply of glutamate and its co-agonist, glycine, have been slower. While the anatomical sources and metabolic compartmentation of glutamate have been studied, limited efforts have been dedicated to defining the dynamics and compartmentation of the co-agonist, glycine. In fact, most investigators have made the assumption that glycine is freely available, via diffusion, for synaptic transmission at NMDA-type synaptic clefts. This assumption ignores the intricate inactivation mechanisms potentially involved in regulating synaptic levels of this amino acid and the recent descriptions of high levels of endogenous D-serine, another potential agonist of the NMDA-associated glycine receptor, in the brain. In this review, the relevance of these data and pharmacological experiments pertinent to the question of whether the NMDA-associated glycine receptor is saturated in vivo or not, is presented.
Wood
P L
PL
Dept. of Pharmacology, CoCensys Inc., Irvine, CA 92718, USA.
D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D018009:Receptors, Glycine / Q000819:agonists* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism; D012694:Serine / Q000378:metabolism / Q000494:pharmacology*
D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D005998:Glycine