L-PHOSPHOSERINE, A METABOLITE ELEVATED IN ALZHEIMERS-DISEASE, INTERACTS WITH SPECIFIC L-GLUTAMATE RECEPTOR SUBTYPES

L-Phosphoserine is one of the phosphomonoesters elevated in Alzheimer's disease brain and has close structural similarity to L-glutamate. This study attempts to define precisely the actions of L-phosphoserine at L-glutamate receptor subtypes. L-Phosphoserine is shown to bind to N-methyl-D-aspartate and kainic acid receptor subtypes, but not to the quisqualic acid subtype. Studies of [H-3]MK-801 binding in the presence and absence of L-glutamate and glycine show L-phosphoserine to be a competitive N-methyl-D-aspartate antagonist. The IC50 of L-phosphoserine in these studies varies from 373 to 721-mu-M. This may indicate a physiologically relevant action of L-phosphoserine in Alzheimer's disease brain because whole brain concentrations may reach over 1 mM.