L-phosphoserine, a metabolite elevated in Alzheimer's 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 [3H]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 microM. This may indicate a physiologically relevant action of L-phosphoserine in Alzheimer's disease brain because whole brain concentrations may reach over 1 mM.
Klunk
W E
WE
Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania.
McClure
R J
RJ
Pettegrew
J W
JW
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D016291:Dizocilpine Maleate / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D007608:Kainic Acid / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D010768:Phosphoserine / Q000378:metabolism*; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D010768:Phosphoserine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid; D005998:Glycine