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Effect of AA‐861, a 5‐Lipoxygenase Inhibitor, on Leukotriene Synthesis in Human Polymorphonuclear Leukocytes and on Cyclooxygenase and 12‐Lipoxygenase Activities in Human Platelets
Author(s) -
Mita H.,
Yui Y.,
Shida T.
Publication year - 1986
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.1986.tb00334.x
Subject(s) - leukotriene , leukotriene b4 , cyclooxygenase , arachidonate 5 lipoxygenase , arachidonic acid , lipoxygenase , leukotriene c4 , histamine , platelet , leukotriene d4 , chemistry , biochemistry , pharmacology , biology , immunology , enzyme , inflammation , asthma
AA‐861, a selective inhibitor of 5‐lipoxygenase of arachidonic acid, was tested for ability to inhibit leukotriene C 4 and leukotriene B 4 synthesis in human polymorphonuclear leukocytes after calcium ionophore stimulation. AA‐861 dose‐dependently inhibited leukotriene B 4 and leukotriene C 4 generation in human polymorphonuclear leukocytes; the concentration required to inhibit generation by 50 % (IC 50 ) was 3 × 10 −7 M for leukotriene B 4 and 1 × 10 −8 M for leukotriene C 4 . BW‐755C inhibited the generation of leukotriene C 4 with an IC 50 of about 10 −5 M, indicating that AA‐861 is about 1000 times more potent than BW‐755C. AA‐861 did not affect the activity‐ of either cyclooxygenase or 12‐lipoxygenase at a concentration up to 10 −5 M in human platelets. AA‐861 did not inhibit histamine release from human basophils. These results indicate that AA‐861 selectively inhibits 5‐lipoxygenase but not cyclooxygenase or 12‐lipoxygenase in human specimens.