A pharmacologic analysis of the action of platelet-activating factor in the induction of hindpaw edema in the rat.
Platelet-activating factor (PAF), a phospholipid product of neutrophils, alveolar macrophages, monocytes, and platelets and an important mediator of inflammatory reactions, was studied for its ability to evoke hindpaw edema in the rat. PAF caused edema, peaking at 1 hr and gradually declining over the next 2 hr. The H1 and H2 antihistamines, mepyramine and cimetidine, the serotonin/histamine antagonist, cyproheptadine, and the serotonin antagonist, methysergide, were ineffective in reducing PAF-induced paw edema. Indomethacin, acetylsalicylic acid, and dexamethasone did not inhibit the peak edematous response but significant reduction was noted with only dexamethasone at 3 hr. Prazosin and propranolol did not prevent PAF-induced edema, whereas, yohimbine, phentolamine, rauwolscine, verapamil and theophylline partially inhibited edema. Clonidine and guanfacine did not induce edema when injected into the rat hindpaw. These results suggest that PAF elicits edema at vascular sites of the rat hindpaw which are partially dependent on extracellular Ca2+ movement, are not due to alpha-1 or alpha-2-adrenoreceptor stimulation, histamine, serotonin, or prostaglandin activity, and demonstrates variable sensitivities to agents blocking Ca2+ entry. Inhibition of specific PAF-sensitive receptors await the discovery of specific PAF antagonists.
D000818:Animals; D002351:Carrageenan; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000503:physiopathology*; D006614:Hindlimb; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000098:blood supply*; D010646:Phentolamine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D010972:Platelet Activating Factor; D015016:Yohimbine; D003907:Dexamethasone; D002351:Carrageenan; D013806:Theophylline; D014700:Verapamil; D007213:Indomethacin; D010646:Phentolamine