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.
Zabøocka
B
B
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
Domańska-Janik
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001224:Aspartic Acid / Q000037:antagonists & inhibitors*; D002545:Brain Ischemia / Q000378:metabolism*; D004224:Diterpenes; D004789:Enzyme Activation; D046934:Ginkgolides; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D004224:Diterpenes; D046934:Ginkgolides; D007546:Isoquinolines; D007783:Lactones; D010879:Piperazines; D010972:Platelet Activating Factor; D014316:Tritium; D001224:Aspartic Acid; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C045856:ginkgolide B; D011493:Protein Kinase C; D011188:Potassium