PAF ANTAGONIST, BN52021, INHIBITS [H-3] D-ASPARTATE RELEASE AFTER ISCHEMIA IN-VITRO

THE effect of the platelet activating factor (PAF) antagonist BN52021 on [H-3]D-aspartate (D-Asp) release was investigated in rat hippocampa l slices during and after incubation (20 min) in ischaemia-like condit ions. Ischaemia did not influence spontaneous D-Asp outflow whereas K-evoked, calcium-dependent release was markedly enhanced in reoxygenat ed, post-ischaemic slices. These slices also showed a substantial tran slocation/activation of protein kinase C (PKC). BN52021 blocked both i schaemia-induced effects, Moreover, the PKC inhibitor H7 attenuated po st-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 act ivation proceeds to enhanced glutamate exocytosis, we speculate on the involvement of PAF receptor stimulation in the pathology of cerebral ischaemia.