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 the AMPA (alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) subtypes of glutamate receptors were analyzed by quantitative autoradiography of [H-3]AMPA, [H-3]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and [H-3]glutamate binding on rat brain tissue sections. Preincubation of brain sections with PS produced an increase 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 different in various brain structures, being larger in the molecular layer of 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 suggests that both treatments share a common mechanism(s) for producing increased agonist binding. Finally, the effect of PS on AMPA receptor properties was markedly reduced in rat brain sections prepared from neonatal rats at a developmental stage that is normally characterized by the absence of LTP expression in certain brain regions. The present data are consistent with the hypothesis that alteration in the lipid composition of synaptic membranes may be an important mechanism for regulating AMPA receptor properties, which could be involved in producing long-lasting changes in synaptic operation.