Uses
MK-571 sodium salt hydrate has been used:
- as an efflux inhibitor for monitoring multidrug resistance protein (MRP)-function and to avoid redundancy of other transporters
- to assess its effect on cell proliferation and 2D-migration in vitro in various cell lines of glioblastoma multiforme (GBM)
- as multidrug resistance (MDR) transporter inhibitor to study its effects in ovarian cancer cells
- as specific inhibitors of ABCC1/2 to investigate transport, toxicity, flow cytometry and arsenic efflux
Biological Activity
mk571 sodium salt is a specific cyslt1 (cysteinyl-leukotriene type 1 receptor) antagonist [1].cysteinyl leukotriene receptor 1, also termed as cysltr1, is a receptor for cysteinyl leukotrienes (lt)which mediates a large variety of allergic and hypersensitivity reactions in humans [2].
Biochem/physiol Actions
MK 571 is a potent and selective leukotriene D4 (LTD4) antagonist and ABCC multidrug resistance protein 1(MRP1) inhibitor. The cysteinyl leukotrienes (CysLTs), LTC4, LTD4, and LTE4, mediate their actions through two distinct G-protein coupled receptors. LTD4 is the preferred ligand for the CysLT1 receptor, whereas LTC4 and LTD4 bind with approximately equal affinity to the CysLT2 receptor. MK 571 is a selective, orally active CysLT1 receptor antagonist. It blocks the binding of LTD4, but not LTC4, to human and guinea pig lung membranes with Ki values of 0.22 nM and 2.1 nM, respectively. MK 571 effectively blocks LTD4 activation of recombinant human and mouse CysLT1 receptors but is ineffective at blocking LTC4 or LTD4 activation of the recombinant human or murine CysLT2 receptors. It potentially inhibits MRP1 and has been shown to overcome acquired arsenic tolerance.
in vitro
mk571 is a multidrug resistance protein-2 (abcc2, mrp2) inhibitor and had been widely used to demonstrate the role of mrp2 in the cellular efflux of drugs, xenobiotics and their conjugates. apically-applied mk571 resulted in significant reductions in both the apical and basolateral efflux of flavonol conjugates from caco-2/tc7 monolayers. the estimated ki for inhibition of the synthesis of k-4′-o-glca by mk571 is 19.7 μm. mk571 inhibited the intracellular biosynthesis of all flavonol glucuronides and sulphates by caco-2 cells in a dose-dependent manner. mk571 significantly inhibited phase-2 conjugation of kaempferol by cell-free extracts of caco-2, and competitively inhibited the production of kaempferol-4′-o-glucuronide. these data indicated that mk571, in addition to inhibiting mrp2, was a potential inhibitor of enterocyte phase-2 conjugation [3].
References
[1]. thivierge m, turcotte s, rola-pleszczynski m, et al. enhanced cysteinyl-leukotriene type 1 receptor expression in t cells from house dust mite-allergic individuals following stimulation with der p[j]. journal of immunology research, 2015, 2015.
[2]. singh rk, tandon r, dastidar sg, ray a (november 2013). "a review on leukotrienes and their receptors with reference to asthma". the journal of asthma. 50 (9): 922–31.
[3]. barrington r d, needs p w, williamson g, et al. mk571 inhibits phase-2 conjugation of flavonols by caco-2/tc7 cells, but does not specifically inhibit their apical efflux[j]. biochemical pharmacology, 2015, 95(3): 193-200.
