Postnatal changes in AMPA receptor regulation by phospholipase A2 treatment of synaptic membranes: temporally differential effects on agonist and antagonist binding.

Previous results have indicated that phospholipase A2 (PLA2) treatment of telencephalic membranes produced opposite effects on 3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding in neonatal and adult rats. In the present study, we compared the effects of PLA2 treatment of telencephalic membranes on the binding characteristics of agonists and antagonists of the AMPA receptors in the developing rat brain. Whereas PLA2 treatment of telencephalic membranes from postnatal day (PND) 5 and 10 animals produced an important decrease in 3H]AMPA binding, the same treatment performed on PND 20, 25 and adult membranes resulted in a marked increase in 3H]AMPA binding; the shift from decreased to increased 3H]AMPA binding occurred at about PND 15. In contrast to 3H]AMPA binding, 3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) binding was substantially reduced following PLA2 treatment at PND 5, 10 and 20, and effect due to a decrease in the maximal number of 3H]CNQX binding sites. In adult membranes, the effect of PLA2 treatment on 3H]CNQX binding was markedly reduced when compared to neonatal membranes. Pretreatment of synaptic membranes with PCMBS (a sulfhydryl reagent) increased 3H]AMPA binding in both young (PND 10) and adult telencephalic membranes, without significantly changing 3H]CNQX binding. The various effects of PLA2 treatment on agonist and antagonist binding did not appear to be due to major differences in the pharmacological properties of the AMPA receptors at different ages. The present results indicate that the characteristics of the binding sites for agonists and antagonists of the AMPA receptors are differentially modulated by the lipid environment during the postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)