EFFECT OF PHOSPHATIDYLSERINE ON THE BINDING-PROPERTIES OF GLUTAMATE RECEPTORS IN BRAIN SECTIONS FROM ADULT AND NEONATAL RATS

The effects of phosphatidylserine (PS) on the binding properties of th e AMPA (alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid) and NMD A (N-methyl-D-aspartate) subtypes of glutamate receptors were analyzed by quantitative autoradiography of [H-3]AMPA, [H-3]6-cyano-7-nitroqui noxaline-2,3-dione (CNQX) and [H-3]glutamate binding on rat brain tiss ue sections. Preincubation of brain sections with PS produced an incre ase in [H-3]AMPA binding without modifying the binding properties of [ H-3]CNQX, an antagonist of AMPA receptors. This effect of PS appeared to be specific for the AMPA subtype of glutamate receptors as the same treatment did not modify [H-3]glutamate binding to the NMDA receptors . Furthermore, the PS-induced increase in [H-3]AMPA binding was differ ent in various brain structures, being larger in the molecular layer o f the cerebellum and almost absent in the striatum. Preincubation with calcium also augmented [H-3]AMPA binding, and the lack of additivity of the effects of calcium and PS on [H-3]AMPA binding strongly suggest s that both treatments share a common mechanism(s) for producing incre ased agonist binding. Finally, the effect of PS on AMPA receptor prope rties was markedly reduced in rat brain sections prepared from neonata l rats at a developmental stage that is normally characterized by the absence of LTP expression in certain brain regions. The present data a re consistent with the hypothesis that alteration in the lipid composi tion of synaptic membranes may be an important mechanism for regulatin g AMPA receptor properties, which could be involved in producing long- lasting changes in synaptic operation.