Functional coupling of cyclooxygenase 1 and 2 to discrete prostanoid synthases in liver macrophages.
The profile of released prostanoids after addition of exogenous arachidonic acid to resident liver macrophages is different from the profile obtained in lipopolysaccharide-pretreated cells. In resident and lipopolysaccharide-pretreated cells, AA leads to a release of thromboxane B(2), prostaglandin F(2alpha), E(2), and D(2). A specifically enhanced formation of prostaglandin E(2) is obtained in lipopolysaccharide-pretreated cells. Resident liver macrophages express cyclooxygenase 1, and thromboxane A(2)-, prostaglandin F(2alpha)-, E(2)-, and D(2)-synthase. Treatment with lipopolysaccharide induces-in addition to cyclooxygenase 2-an enhanced expression of the prostaglandin E(2) synthase. In resident liver macrophages, the formation of prostanoids from exogenous arachidonic acid is completely inhibited by SC560 (a specific inhibitor of cyclooxygenase 1), but remains unchanged with SC236 (a specific inhibitor of cyclooxygenase 2). In lipopolysaccharide-pretreated liver macrophages, the formation of thromboxane B(2), prostaglandin F(2alpha) and D(2) is equally inhibited by SC560 and SC236 by about 50%. In contrast, the formation of prostaglandin E(2) is inhibited to a greater extent by SC560 (75%) compared to SC236 (26%). We conclude from these data, that in lipopolysaccharide-pretreated liver macrophages (i) cyclooxygenase 1 and 2 couple both to discrete prostanoid synthases, (ii) the functional coupling of cyclooxygenase 1 and 2 to the thromboxane A(2)-, prostaglandin F(2alpha)-, and D(2)-synthase is almost identical, and (iii) the enhanced prostaglandin E(2) synthesis is due to an enhanced expression of the prostaglandin E(2) synthase, which is coupled more efficiently to cyclooxygenase 1.
Dieter
P
P
Medical Faculty Carl Gustav Carus, Institute of Physiological Chemistry, Technical University Dresden, Fetscherstrasse 74, Dresden, D-01307, Germany.
Scheibe
R
R
Jakobsson
P J
PJ
Watanabe
K
K
Kolada
A
A
Kamionka
S
S
D000818:Animals; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007527:Isoenzymes / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D008264:Macrophages / Q000201:enzymology* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011453:Prostaglandins; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; D015230:Prostaglandin D2