PAF antagonist, BN52021, inhibits [3H]D-aspartate release after ischaemia in vitro

The effect of the platelet activating factor (PAF) antagonist BN52021 on [3H]D-aspartate (D-Asp) release was investigated in rat hippocampal slices during and after incubation (20 min) in ischaemia-like conditions. Ischaemia did not influence spontaneous D-Asp outflow whereas K(+)-evoked, calcium-dependent release was markedly enhanced in reoxygenated, post-ischaemic slices. These slices also showed a substantial translocation/activation of protein kinase C (PKC). BN52021 blocked both ischaemia-induced effects. Moreover, the PKC inhibitor H7 attenuated post-ischaemic K(+)-evoked D-Asp release when beta-PDBu, a PKC activator, was used to enhance the response of normoxic slices. Assuming that PKC is activated by ischaemia in a PAF-dependent manner and that this activation proceeds to enhanced glutamate exocytosis, we speculate on the involvement of PAF receptor stimulation in the pathology of cerebral ischaemia.