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 greater than TZI-2721 greater than NDGA greater than AA861 greater than FPL55712 greater than isoproterenol; rat 5-LO, 5-HDHDMF greater than AA861 greater than TZI-2721 greater than NDGA greater than FPL55712 greater than KP-136 greater than MCI-826 greater than benoxaprofen; and rabbit 5-LO, 5-HDHDMF greater than TZI-2721 greater than NDGA greater than AA861 greater than FPL55712 greater than KP-136 greater than MCI-826. The 5-LO activity from the rhesus monkey was dose-dependently inhibited by only 3 compounds, 5-HDHDMF greater than NDGA greater than 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 greater than 5-HDHDMF greater than NDGA greater than AA861 greater than FPL55712. From these results, it was strongly suggested that there is a species difference of this enzyme in its sensitivity to drugs.
Okumura
M
M
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Obata
N
N
Yamamura
H
H
Kohno
S
S
Ohata
K
K
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D016859:Lipoxygenase Inhibitors; D008253:Macaca mulatta; D008297:Male; D009504:Neutrophils / Q000201:enzymology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D007202:Indicators and Reagents; D016859:Lipoxygenase Inhibitors; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase