Species Difference of 5-Lipoxygenase Derived from Polymorphonuclear Leukocytes on Sensitivity to Drugs

Effects of 12 compounds including 5-lipoxygenase (5-LO) inhibitors and antiallergic drugs on the activity of 5-LO from the polymorphonuclear leukocytes (PMN) of guinea pigs, rats, rabbits, monkeys and humans were examined. The 5-LO activity was inhibited by the drugs according to the following orders of efficacy：Guinea pig 5-LO, 5-HDHDMF>TZI-2721>NDGA>AA861>FPL55712>isoproterenol; rat 5-LO, 5-HDHDMF>AA861>TZI-2721>NDGA>FPL55712>KP-136>MCI-826>benoxaprofen; and rabbit 5-LO, 5-HDHDMF>TZI-2721>NDGA>AA861>FPL55712>KP-136>MCI-826. The 5-LO activity from the rhesus monkey was dose-dependently inhibited by only 3 compounds. 5-HDHDMF>NDGA>TZI-2721, in this order, but the other compounds, except for AA861, did not show any effect on this activity. In humans, 5-LO activity was inhibited in the following order： TZI-2721>5-HDHDMF>NDGA>AA861>FPL55712. From these results, it was strongly suggested that there is a species difference of this enzyme in its sensitivity to drugs.