-2-[4-(QUINOLIN-2-YL-METHOXY)PHENYL]-2-CYCLOPENTYL ACETIC-ACID (BAY X1005), A POTENT LEUKOTRIENE SYNTHESIS INHIBITOR - EFFECTS ON ANTI-LGE CHALLENGE IN HUMAN AIRWAYS

Anti-IgE at a fixed dilution (1:1000) contracted human airways that ha d been pretreated with atropine(l mu M), indomethacin (3 mu M) and chl orpheniramine (1 mu M). This response was blocked by the potent leukot riene synthesis inhibitor BAY x1005 -2-[4-(Quinolin-2-yl-methoxy)pheny l}-2-cyclopentyl acetic acid]. The leukotriene synthesis inhibitor MK- 886 also blocked the contraction, but BAY x1005 was approximately 10-f old more potent than MK-886 (the IC50 values were 0.27 mu M and 3.4 mu M for BAY x1005 and MK-886, respectively). BAY x1005 (1 mu M) did not alter LTD(4) cumulative concentration-effect curves on human airways. Bronchial muscles derived from different levels of the respiratory tr act released small quantities of LTE(4) (proximal, 7.99 +/- 1.25 ng/g tissue wet wt.; distal, 13.12 +/- 4.46 ng/g tissue wet wt.). These bas al levels were significantly increased when the preparations were chal lenged with a fixed dilution (1:1000) of anti-IgE (proximal, 21.84 +/- 5.33 ng/g tissue wet wt.; distal 72.13 +/- 30.70 ng/g tissue wet wt.) . Indomethacin (3 mu M) did not alter either the basal amounts or the levels of LTE(4) measured during anti-IgE stimulation. However, BAY x1 005 or MK-886 in the presence of indomethacin prevented the increase i n LTE(4) levels that were observed during anti-IgE challenge. In these protocols the IC50 values obtained were 0.18 mu M and 1.42 mu M for B AY x1005 and MK-886, respectively. These data demonstrate that BAY x10 05 is a potent leukotriene synthesis inhibitor in human airways.