Characterization of the human cysteinyl leukotriene 2 receptor

J Biol Chem. 2000 Sep 29;275(39):30531-6. doi: 10.1074/jbc.M003490200.


The contractile and inflammatory actions of the cysteinyl leukotrienes (CysLTs), LTC(4), LTD(4), and LTE(4), are thought to be mediated through at least two distinct but related CysLT G protein-coupled receptors. The human CysLT(1) receptor has been recently cloned and characterized. We describe here the cloning and characterization of the second cysteinyl leukotriene receptor, CysLT(2), a 346-amino acid protein with 38% amino acid identity to the CysLT(1) receptor. The recombinant human CysLT(2) receptor was expressed in Xenopus oocytes and HEK293T cells and shown to couple to elevation of intracellular calcium when activated by LTC(4), LTD(4), or LTE(4). Analyses of radiolabeled LTD(4) binding to the recombinant CysLT(2) receptor demonstrated high affinity binding and a rank order of potency for competition of LTC(4) = LTD(4) LTE(4). In contrast to the dual CysLT(1)/CysLT(2) antagonist, BAY u9773, the CysLT(1) receptor-selective antagonists MK-571, montelukast (Singulair(TM)), zafirlukast (Accolate(TM)), and pranlukast (Onon(TM)) exhibited low potency in competition for LTD(4) binding and as antagonists of CysLT(2) receptor signaling. CysLT(2) receptor mRNA was detected in lung macrophages and airway smooth muscle, cardiac Purkinje cells, adrenal medulla cells, peripheral blood leukocytes, and brain, and the receptor gene was mapped to chromosome 13q14, a region linked to atopic asthma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Medulla / chemistry
  • Cloning, Molecular
  • Cysteine*
  • Humans
  • Leukotriene Antagonists / pharmacology
  • Leukotriene C4 / metabolism
  • Leukotriene D4 / metabolism
  • Leukotriene E4 / metabolism
  • Leukotrienes / metabolism*
  • Lung / chemistry
  • Membrane Proteins*
  • Models, Molecular
  • Myocardium / chemistry
  • Receptors, Leukotriene / blood
  • Receptors, Leukotriene / genetics*
  • Receptors, Leukotriene / metabolism*
  • Recombinant Proteins / metabolism
  • SRS-A / analogs & derivatives
  • SRS-A / pharmacology
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Tissue Distribution


  • BAY u9773
  • Leukotriene Antagonists
  • Leukotrienes
  • Membrane Proteins
  • Receptors, Leukotriene
  • Recombinant Proteins
  • SRS-A
  • Leukotriene C4
  • Leukotriene D4
  • Leukotriene E4
  • cysteinyl leukotriene receptor 2
  • Cysteine