Ex vivo effects of nonsteroidal antiinflammatory drugs on arachidonic acid metabolism in neutrophils from a reverse passive Arthus reaction.
Rat neutrophils isolated from 4-h reverse passive Arthus reaction (RPAR) pleural exudates actively metabolize arachidonic acid via cyclooxygenase and lipoxygenase. Utilizing this system, the effect of oral doses of nonsteroidal antiinflammatory drugs on the ability of these cells to produce HHT, 5-HETE, and LTB from exogenously added arachidonic acid has been investigated. In vitro and ex vivo, indomethacin and timegadine inhibit cyclooxygenase activity in rat pleural neutrophils. In vitro, timegadine is a lipoxygenase as well as a cyclooxygenase inhibitor. This dual inhibition is confirmed by the observation that ex vivo timegadine inhibits the production of lipoxygenase as well as cyclooxygenase metabolites. While indomethacin, a cyclooxygenase inhibitor, primarily inhibits edema formation, the inhibition of both pathways of arachidonic acid metabolism by timegadine is reflected in the drug's ability to reduce cellular influx as well as edema formation in the RPAR pleural cavity inflammatory reaction.
Myers
R F
RF
Anthes
J C
JC
Casmer
C J
CJ
Siegel
M I
MI
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001183:Arthus Reaction / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology; D004487:Edema / Q000209:etiology; D006146:Guanidines / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000150:complications; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D006146:Guanidines; C028998:timegadine; D016718:Arachidonic Acid; D000001:Calcimycin; D007213:Indomethacin