Translocation of HL-60 cell 5-lipoxygenase. Inhibition of A23187- or N-formyl-methionyl-leucyl-phenylalanine-induced translocation by indole and quinoline leukotriene synthesis inhibitors.
We have demonstrated translocation of HL-60 cell 5-lipoxygenase to a membrane compartment in response to both the calcium ionophore A23187 and the receptor-mediated stimulus, N-formyl-methionyl-leucyl-phenylalanine (fMLP). In addition, we have shown inhibition of A23187- and fMLP-induced 5-lipoxygenase translocation by an indole and a quinoline leukotriene synthesis inhibitor, MK-886 and L-674,573, respectively. Selectivity of inhibition of 5-lipoxygenase translocation in both fMLP- or A23187-challenged cells is shown using the indole L-583,916 and quinoline L-671,480, which neither inhibit leukotriene synthesis nor inhibit 5-lipoxygenase translocation. The present study in HL-60 cells is the first demonstration of the selective inhibition of 5-lipoxygenase translocation by quinoline leukotriene synthesis inhibitors, exemplified by L-674,573. Also described here is the first demonstration of 5-lipoxygenase translocation and inhibition in response to a stimulus other than A23187, namely the receptor-mediated stimulus, fMLP.
Kargman
S
S
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada.
Prasit
P
P
Evans
J F
JF
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000096:biosynthesis* / Q000302:isolation & purification; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000201:enzymology; D002722:Chlorobenzenes
D001094:Arachidonate 5-Lipoxygenase; D000001:Calcimycin; D004121:Dimethyl Sulfoxide; D007211:Indoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011804:Quinolines; C060893:MK-886; D002722:Chlorobenzenes; C071988:L 674573