LTD 4 0.22 nM (Ki, In guinea pig lung) LTD 4 2.1 nM (Ki, In human lung)

MK-571 (L-660,711; i.v.) antagonizes bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC 4 , LTD 4 , and LTE 4 but does not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal MK-571 antagonizes LTD 4 (0.2-12.8 μg/kg)-induced bronchoconstriction in guinea pigs, and p.o. MK-571 blockes LTD 4 - and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 μg/kg). Hypoxia-exposed WT mice are treated with either saline or MK-571 (5 mg/kg/d or 25 mg/kg/d) for 2 more weeks while being maintain in hypoxic conditions. Saline-treated mice display all the hallmarks of PH (i.e., an increase in RVSP, Fulton index, and arterial wall thickness). However, following hypoxia, MK-571-treated mice display lower RVSP and Fulton index and a decrease in the medial thickening of small pulmonary arteries and arterioles.

MK-571 (L660,711) is a potent and selective competitive inhibitor of [ 3 H]leukotriene D4 binding in guinea pig (K i value, 0.22 nM) and human (K i value, 2.1 nM) lung membranes. MK-571 is essentially inactive versus [ 3 H]LTC4 binding with IC 50 values of 23±11 μM (n=16) and 32 μM (n=1) in guinea pig and human lung, respectively. MK-571 competitively antagonizes contractions of guinea pig trachea and ileum induced by leukotriene (LT) D 4 (respective pA 2 values, 9.4 and 10.5) and LTE4 (respective pA 2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD 4 (pA 2 value, 8.5). MK-571 (58 nM) antagonizes contractions of guinea pig trachea induced by LTC 4 in the absence (dose ratio=28) but not in the presence of 45 mM L-serine borate (dose ratio less than 2). MK-571 (19μM) does not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF 2 alpha, U-44069, or PGD 2 . In the presence of atropine, mepyramine, and indomethacin, MK-571 (19 μM) inhibits a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea.

MK-571 sodium salt是一种选择性，口服活性的白三烯D4受体拮抗剂，在豚鼠和人肺膜的Ki分别为0.22 和 2.1 nM。