MELITTIN INCREASES AMPA RECEPTOR AFFINITY IN RAT-BRAIN SYNAPTONEUROSOMES

Recent experimental evidence suggests that phospholipase-induced chang es in binding properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxa zol propionate (AMPA) subtype of glutamate receptors account for the i ncrease in synaptic response observed in long-term potentiation (LTP). In the present study, we report that treatment of rat telencephalic s ynaptoneurosomes with the bee venom peptide melittin, a potent activat or of endogenous phospholipases, increased [H-3]AMPA binding to the AM PA receptor. The action of melittin was concentration-dependent (EC(50 ) value = 10 mu g/ml) and did not require the presence of extracellula r calcium. Saturation kinetic experiments revealed that the increase i n [H-3]AMPA binding produced by melittin was due to an enhancement in the affinity of the AMPA receptor, an effect markedly reduced by the p hospholipase A(2) (PLA(2)) inhibitor bromophenacyl bromide (BPB). In c ontrast to BPB, inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism did not interfere with the melittin-in duced increase in [H-3]AMPA binding. In neonatal synaptoneurosomes, th e effect of melittin on [H-3]AMPA binding was significantly reduced wh en compared to adult synaptoneurosomes, an effect which is consistent with the observation that LTP is not present in very young animals. Th e results indicate that activation of endogenous phospholipases may be an important mechanism in the regulation of AMPA receptor properties in LTP.