PLA2-induced oedema in rat skin and histamine release in rat mast cells. Evidence for involvement of lysophospholipids in the mechanism of action.
Injection of phospholipase A2 (PLA2) in the rat skin produced a significant rise in oedema, which was inhibited by the simultaneous coinjection of aristolochic acid (100 micrograms), mepacrine (100 micrograms) and p-bromophenacyl bromide (10 micrograms). Indomethacin, nordihydroguaiaretic acid and WEB 2086 were without inhibitory effect on this model, whereas dexamethasone (5 mg/kg, p.o.) and coinjection of chlorpheniramine (20 micrograms) inhibited the oedema formation by more than 60%. Dose-dependent histamine release by rat peritoneal cells was induced by PLA2 and by lysophosphatidylserine and this effect could be antagonized by aristolochic acid and mepacrine. Apomorphine, previously reported to be an antagonist at lysophospholipid receptors, was able to inhibit the histamine release by mast cells as well as the oedema formation in rat skin. Taken all together, these results suggest that lysophospholipids, produced by the action of PLA2, are the mediators for the histamine release in rat peritoneal cells and could play an important role in the early oedema development in rat skin after PLA2 administration.
Moreno
J J
JJ
R & D Department, Laboratorios Menarini S.A., Badalona, Spain.
Ferrer
X
X
Ortega
E
E
Carganico
G
G
D000818:Animals; D034341:Aristolochic Acids; D003594:Cytoplasmic Granules / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000166:cytology / Q000187:drug effects
D034341:Aristolochic Acids; D008246:Lysophospholipids; D010616:Phenanthrenes; D003907:Dexamethasone; C000228:aristolochic acid I; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D007213:Indomethacin