PAF-acether-induced plasma exudation in rat skin is independent of platelets and neutrophils.
The ability of Paf-acether to induce increased plasma protein extravasation (IPPE) was assessed in the skin of rats by measuring extravasation of 125I-bovine serum albumin. Paf-acether elicited dose-dependent IPPE with a threshold of 0.04 pmol and a maximum at 4.5 nmol, with an effective concentration (EC50) of 23 pmol. The EC50 of the 1-0-ester Paf-acether analog was 1.5 nmol whereas 2-lyso Paf-acether was ineffective in inducing IPPE. Serotonin and histamine were respectively 100 and 1,00-fold less potent than Paf-acether. High doses of Paf-acether also resulted in a dose related accumulation of III-indium oxine labeled platelets. Ultrastructural and radioisotopic studies showed that Paf-acether-induced IPPE was not dependent upon platelet accumulation. In addition, platelet release products were ruled out in this phenomenon, since a "cocktail" of indomethacin, methysergide and pyrilamine-maleate failed to significantly reduce Paf-acether-induced IPPE. Neutrophils were not involved in Paf-acether -induced IPPE since nitrogen mustard-treated animals presented with IPPE not significantly different from controls. Finally, the specificity of Paf-acether on IPPE formation was demonstrated by its complete prevention by prior intravenous injection of Paf-acether (6 ug/kg), but not of Paf-acether analogs, histamine or serotonin.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008854:Microscopy, Electron; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism*
D001798:Blood Proteins; D010972:Platelet Activating Factor; D011738:Pyrilamine; D007213:Indomethacin; D008784:Methysergide