Prostaglandin H Synthase of Mouse Macrophages: Inhibiting and Activating Action of Ibuprofen

M. G. Sergeeva,^1,2 M. V. Gonchar,¹ D. A. Namgaladze,¹ A. T. Mevkh,¹ and S. D. Varfolomeyev¹

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (7-095) 939-31-81; E-mail: mgserg@pghs.genebee.msu.su

²To whom correspondence should be addressed.

Submitted September 5, 1996; revision submitted October 31, 1996.

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 10⁶ cells), PGF_2alpha (120 ± 15 ng per 10⁶ cells), and TxB₂ (48 ± 5 ng per 10⁶ cells). Incubation of the macrophages with 10^-12 M ibuprofen leads to a sharp increase of PGE₂ and PGF_2alpha synthesis (315 ± 84 and 320 ± 20 ng per 10⁶ 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 (K_m = 5.3·10^-5 M, IC_50,ibuprofen = 15 µM). Some particularities of the PGH-synthase constitutive isoform (PGH-synthase-1) cellular regulation are discussed.

KEY WORDS: prostaglandin H synthase, peritoneal macrophages, ibuprofen, arachidonic acid, prostanoids.

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