Sulfidopeptide-leukotrienes are major mediators of arachidonic acid-induced mouse ear edema.
The inflammatory response of the mouse ear to topical application of arachidonic acid (2 mg/ear) was examined to study the roles of sulfidopeptide-leukotrienes (LTs) and prostaglandin (PG) E2 as mediators of edema. The increase in ear thickness caused by arachidonic acid (AA) (edema), reached a maximum at 45 to 60 min after AA application. The amounts of immunoreactive LTC4 and immunoreactive PGE2 produced increased significantly in 5 to 10 min, and then diminished gradually over 60 min. 5-lipoxygenase inhibitors, dual cyclooxygenase/lipoxygenase inhibitors and anti-histamines significantly inhibited AA-induced ear edema. Both production of PGE2 and LTC4 were suppressed by NDGA at 1 mg/ear which also inhibited ear swelling. However aspirin, which enhanced LTC4 production in AA-induced ear edema did not inhibit the ear swelling. Hypodermic injection of LTC4 at 25 ng or PGE2 at 500 ng/ear did not cause swelling, but edema was induced when both compounds were injected simultaneously. Moreover ear swelling was induced by injection of both LTD4 at 50 ng and PGE2 at 500 ng/ear. Furthermore, concomitant injection of histamine, at 500 ng or serotonin at 50 ng/ear with LTC4 at 25 ng caused ear swelling but both compounds at the same dose alone did not induce swelling. These results suggest that AA-induced ear edema is predominantly mediated by LTC4 and other lipoxygenase products while PGE2 (in the presence of LTs) acts to facilitated ear swelling, although serotonin and histamine may also contribute.
Inoue
H
H
Research Laboratory, Minophagen Pharmaceutical Co., Kanagawa, Japan.
Mori
T
T
Koshihara
Y
Y
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology*; D006632:Histamine / Q000494:pharmacology; D007700:Kinetics; D015289:Leukotrienes / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*; D012701:Serotonin / Q000494:pharmacology
D001095:Arachidonic Acids; D015289:Leukotrienes; D013189:SRS-A; D016718:Arachidonic Acid; D012701:Serotonin; D006632:Histamine; D015232:Dinoprostone