Desensitization and antagonism of rat polymorphonuclear leukocytes stimulated with PAF acether

The activation of rat polymorphonuclear leukocytes (PMN) with PAF-acether (platelet-activating factor) was blocked by two antagonists: 48740 RP and BN 52021. The release of beta glucuronidase was usually better inhibited than that of lysozyme suggesting that the tested antagonists interfere rather with PAF-acether exocytosis of azurophil granules. Inhibition was relatively specific, even though a moderate effect (below 34%) upon PMN activation by the two unrelated agonist n-formyl-Methionyl-Leucyl-Phenylalanine (fMLP) and leukotriene B4 sometimes reached significance. The partial persistence of inhibition to stimulation with PAF-acether after elimination of both inhibitors suggests that they do not act at the PAF-acether receptor only. Furthermore, the observation of cross desensitization between PAF-acether and fMLP may be related to common pathways and/or metabolites, including PAF-acether itself.