小鼠巨噬细胞的前列腺素H合酶：布洛芬的抑制和激活作用

Prostaglandin H synthase of mouse macrophages: inhibiting and activating action of ibuprofen.

作者信息

Sergeeva M G, Gonchar M V, Namgaladze D A, Mevkh A T, Varfolomeyev S D

机构信息

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia.

出版信息

Biochemistry (Mosc). 1997 Mar;62(3):269-74.

PMID:9275299

Abstract

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.

摘要

研究了低浓度（10^(-10)-10^(-14)M）布洛芬对含有前列腺素H合酶组成型同工型的小鼠腹腔巨噬细胞释放标记花生四烯酸代谢物的影响。结果发现，在激活过程中，细胞通过环氧化酶途径代谢花生四烯酸，合成PGE2（每10^6个细胞110±10ng）、PGF(2α)（每10^6个细胞120±15ng）和TxB2（每10^6个细胞48±5ng）。巨噬细胞与10^(-12)M布洛芬孵育导致PGf2和PGF(2α)合成急剧增加（分别为每10^6个细胞315±84和320±20ng）。将巨噬细胞PGH合酶的微粒体制剂与公羊精囊的PGH合酶进行比较，并显示了它们性质的相似性（Km = 5.3×10^(-5)M，布洛芬的IC50 = 15μM）。讨论了PGH合酶连续同工型（PGH合酶-1）细胞调节的一些特点。