Betts W H, Hurst N P, Murphy G A, Cleland L G
Rheumatology Unit, Queen Elizabeth Hospital, Woodville, Adelaide, South Australia.
Biochem Pharmacol. 1990 Apr 1;39(7):1233-7. doi: 10.1016/0006-2952(90)90268-p.
The effect of auranofin on the 5-lipoxygenase pathway was studied in human neutrophils stimulated with either fMLP or A23187 (with or without arachidonic acid). The synthesis of leukotriene B4 (LTB4), 5-HETE and the all-trans isomers of LTB4 was measured by HPLC. At low concentrations (0.5-2.0 microM), auranofin stimulated LTB4 synthesis, but inhibited it at higher concentrations (100% inhibition at less than 10 microM). In contrast auranofin caused dose-dependent inhibition of the synthesis of 5-HETE and the all-trans isomers of LTB4. Similar observations were made with each agonist. The stimulation of LTB4 synthesis and inhibition of the trans isomer production suggests that auranofin at low concentrations stimulates LTA hydrolase--the enzyme that converts LTA4 to LTB4, whereas the inhibition of synthesis of all lipoxygenase products at higher auranofin concentrations, suggests inhibition of 5-lipoxygenase/LTA synthase.
研究了金诺芬对用fMLP或A23187（有或没有花生四烯酸）刺激的人中性粒细胞中5-脂氧合酶途径的影响。通过高效液相色谱法测量白三烯B4（LTB4）、5-羟基二十碳四烯酸（5-HETE）和LTB4的全反式异构体的合成。在低浓度（0.5 - 2.0微摩尔）时，金诺芬刺激LTB4合成，但在较高浓度（小于10微摩尔时100%抑制）时抑制其合成。相反，金诺芬对5-HETE和LTB4的全反式异构体的合成产生剂量依赖性抑制。用每种激动剂都得到了类似的观察结果。LTB4合成的刺激和反式异构体产生的抑制表明，低浓度的金诺芬刺激LTA水解酶——将LTA4转化为LTB4的酶，而较高金诺芬浓度下所有脂氧合酶产物合成的抑制表明抑制了5-脂氧合酶/LTA合酶。
