Elsevier

Brain Research

Volume 671, Issue 2, 13 February 1995, Pages 195-200
Brain Research

Melittin increases AMPA receptor affinity in rat brain synaptoneurosomes

https://doi.org/10.1016/0006-8993(94)01313-7Get rights and content

Abstract

Recent experimental evidence suggests that phospholipase-induced changes in binding properties of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors account for the increase in synaptic response observed in long-term potentiation (LTP). In the present study, we report that treatment of rat telencephalic synaptoneurosomes with the bee venom peptide melittin, a potent activator of endogenous phospholipases, increased [3H]AMPA binding to the AMPA receptor. The action of melittin was concentration-dependent (EC50 value = 10 μg/ml) and did not require the presence of extracellular calcium. Saturation kinetic experiments revealed that the increase in [3H]AMPA binding produced by melittin was due to an enhancement in the affinity of the AMPA receptor, an effect markedly reduced by the phospholipase A2 (PLA2) inhibitor bromophenacyl bromide (BPB). In contrast to BPB, inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism did not interfere with the melittin-induced increase in [3H]AMPA binding. In neonatal synaptoneurosomes, the effect of melittin on [3H]AMPA binding was significantly reduced when compared to adult synaptoneurosomes, an effect which is consistent with the observation that LTP is not present in very young animals. The results indicate that activation of endogenous phospholipases may be an important mechanism in the regulation of AMPA receptor properties in LTP.

References (38)

  • MassicotteG. et al.

    Effect of bromophenacylbromide, a phospholipase A2 inhibitor, on the induction and maintenance of LTP in hippocampal slices

    Brain Res.

    (1990)
  • OkadaD. et al.

    Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses

    Neurosci. Lett.

    (1989)
  • ShahiK. et al.

    Glycine-induced changes in synaptic efficacy in hippocampal slices involve changes in AMPA receptors

    Brain Res.

    (1993)
  • ToccoG. et al.

    Long-term potentiation is associated with increased [3H]AMPA binding in rat hippocampus

    Brain Res.

    (1992)
  • ArtolaA. et al.

    Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex

    Nature

    (1990)
  • BaudryM. et al.

    Physiological and pharmacological relationships between long-term potentiation and mammalian memory

    Conc. Neurosci.

    (1992)
  • BaudryM. et al.

    Book Synaptic Plasticity: Molecular, Cellular and Functional Aspects

    (1993)
  • BernardJ. et al.

    The phospholipase A2 inhibitor bromophenacyl bromide prevents the depolarization-induced increase in [3H]AMPA binding in rat brain synaptoneurosomes

    Brain Res.

    (1993)
  • BernardJ. et al.

    Potassium-induced long-term potentiation in area CA1 of the hippocampus involves phospholipase activation

    Hippocampus

    (1994)
  • Cited by (0)

    View full text