Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD4 is released by basophils. Other leukotrienes that function in a similar manner are leukotrienes C4 and E4. Leukotriene receptor antagonists (e.g., zafirlukast, montelukast) inhibit the function of these leukotrienes.
MK-571 is an Orally Active and Selective LTD4 Receptor Antagonist for Asthma Research
MK-571 (L-660711) is an orally active, potent and selective competitive leukotriene D4 (LTD4) receptor antagonist. The Ki values of MK-571 in guinea pig and human lung membranes were 0.22 and 2.1 nM, respectively. It is also a MRP4 and ABCC1 (MRP1) inhibitor. Morever, MK-571 inhibits constitutive and antigen-stimulated S1P (sphingosine-1-phosphate) release.
In Vitro, MK571 (15 μM, 1 h) markedly suppresses constitutive and Ag-stimulated S1P secretion from RBL-2H3 cells and mast cells, and inhibits Fluo-3 efflux. In Vivo, MK-571 (0-0.5 mg/kg, orally, once) produces dose-dependent inhibition of the duration of antigen-induced dyspnea in conscious sensitized rats treated with methysergide (3 μg/kg). What’s more, MK-571 (0-1 mg/kg, orally, once) blocks LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys. In addition, MK-571 (0-25 mg/kg, orally, daily, for 2 more weeks) shows reversal of hypoxic pulmonary hypertension (PH), and protects mice from hypoxic PH.
In conclusion, MK-571 (L-660711) is an orally active, potent and selective competitive leukotriene D4 (LTD4) receptor antagonist for Asthma Research.