Prostaglandin H synthase of mouse macrophages: inhibiting and activating action of ibuprofen.
The effect of low (10(-10)-10(-14 M) ibuprofen concentrations on the release of labeled arachidonic acid metabolites by mouse peritoneal macrophages containing a constitutive isoform of prostaglandin H synthase was investigated. It was found that during the activation the cells metabolized AA through the cyclooxygenase pathway, synthesizing PGE2 (110 +/- 10 ng per 10(6) cells), PGF(2 alpha) (120 +/- 15 ng per 10(6) cells), and TxB2 (48 +/- 5 ng per 10(6) cells). Incubation of the macrophages with 10(-12) M ibuprofen leads to a sharp increase of PGf2 and PGF(2 alpha) synthesis (315 +/- 84 and 320 +/- 20 ng per 10(6) cells, respectively). A microsomal preparation of macrophage PGH-synthase was compared with PGH-synthase of ram seminal vesicles and analogy of their properties was shown (Km = 5.3.10(-5) M, IC50, ibuprofen = 15 microM). Some particularities of the PGH-synthase consecutive isoform (PGH-synthase-1) cellular regulation are discussed.
Sergeeva
M G
MG
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia. mgserg@pghs.genebee.msu.su
Gonchar
M V
MV
Namgaladze
D A
DA
Mevkh
A T
AT
Varfolomeyev
S D
SD
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation; D007052:Ibuprofen / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep
D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007052:Ibuprofen