Inflammatory actions of platelet activating factor (Pafacether) in guinea-pig skin.
Cutaneous responses to synthetic platelet activating factor (Paf-acether) have been studied in guinea-pigs by means of radioisotopic marker techniques. Intradermal injection of Paf-acether elicited increased plasma protein extravasation (IPPE) (0.2-200 pmol/site), platelet accumulation (PA) (20-200 pmol/site) and red blood cell accumulation (RBCA) (200 pmol/site), whereas lyso-Paf (up to 2 nmol/site) was inactive in all these respects. Following intradermal injection, the IPPE responses to Paf-acether (2 and 20 pmol/site) were complete within 15 and 30 min respectively, although in response to 200 pmol/site, IPPE was detectable up to 1.5 h. The PA and RBCA responses to Paf-acether (200 pmol/site) were complete within 1 h. IPPE induced by Paf-acether (3 pmol/site) was potentiated by concomitant intradermal injection of a cutaneous vasodilator prostaglandin E2 (PGE2, 1 nmol/site) and inhibited by the beta-adrenoceptor agonist, isoprenaline (4.5 nmol/site) or the alpha-adrenoceptor agonist, phenylephrine (6 nmol/site). Such observations are consistent with Paf-acether effecting increased vessel wall permeability. Intradermal injection of PGE1 (3 nmol/site) significantly reduced PA in response to Paf-acether (200 pmol/site), whilst significantly enhancing IPPE. This dissociation of increased vascular permeability from PA is consistent with Paf-acether eliciting IPPE via a platelet-independent mechanism. These results indicate that a direct effect on vessel wall permeability contributes to the inflammatory response to Paf-acether in guinea-pig skin. It is suggested that Paf-acether is a potential mediator of allergy and inflammation.
D000527:Alprostadil; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004903:Erythrocyte Aggregation / Q000187:drug effects; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D010972:Platelet Activating Factor; D010974:Platelet Aggregation / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology; D012867:Skin / Q000187:drug effects*
D001798:Blood Proteins; D010972:Platelet Activating Factor; D011458:Prostaglandins E; D000527:Alprostadil