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 ma crophages containing a constitutive isoform of prostaglandin H synthas e was investigated. It was found that during the activation the cells metabolized AA through the cyclooxygenase pathway, synthesizing PGE(2) (110 +/- 10 ng per 10(6) cells), PGF(2 alpha)(120 +/- 15 ng per 10(6) cells), and TxB(2) (48 +/- 5 ng per 10(6) cells). Incubation of the ma crophages with 10(-12) M ibuprofen leads to a sharp increase of PGE(2) and PGF(2 alpha) synthesis (315 +/- 84 and 320 +/- 20 ng per 10(6) ce lls, respectively). A microsomal preparation of macrophage PGH-synthas e was compared with PGH-synthase of ram seminal vesicles and analogy o f their properties was shown (K-m = 5.3.10(-5) M,IC50,ibuprofen = 15 m u M). Some particularities of the PGH-synthase constitutive isoform (P GH-synthase-1) cellular regulation are discussed.