title: Characterization of the human cysteinyl leukotriene 2 receptor.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Heise
authors.forename: B F
authors.initials: BF
authors.lastname: O'Dowd
authors.forename: D J
authors.initials: DJ
authors.lastname: Figueroa
authors.forename: N
authors.initials: N
authors.lastname: Sawyer
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.forename: D S
authors.initials: DS
authors.lastname: Im
authors.forename: R
authors.initials: R
authors.lastname: Stocco
authors.forename: J N
authors.initials: JN
authors.lastname: Bellefeuille
authors.forename: M
authors.initials: M
authors.lastname: Abramovitz
authors.forename: R
authors.initials: R
authors.lastname: Cheng
authors.forename: D L
authors.initials: DL
authors.lastname: Williams
authors.forename: Z
authors.initials: Z
authors.lastname: Zeng
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: M K
authors.initials: MK
authors.lastname: Clements
authors.forename: N
authors.initials: N
authors.lastname: Coulombe
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: C P
authors.initials: CP
authors.lastname: Austin
authors.forename: S R
authors.initials: SR
authors.lastname: George
authors.forename: G P
authors.initials: GP
authors.lastname: O'Neill
authors.forename: K M
authors.initials: KM
authors.lastname: Metters
authors.forename: K R
authors.initials: KR
authors.lastname: Lynch
authors.forename: J F
authors.initials: JF
authors.lastname: Evans
mesh_terms: D000313:Adrenal Medulla / Q000737:chemistry; D003001:Cloning, Molecular; D003545:Cysteine; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism; D017998:Leukotriene D4 / Q000378:metabolism; D017999:Leukotriene E4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008168:Lung / Q000737:chemistry; D008565:Membrane Proteins; D008958:Models, Molecular; D009206:Myocardium / Q000737:chemistry; D018077:Receptors, Leukotriene / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: C071435:BAY u9773; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D011994:Recombinant Proteins; D013189:SRS-A; D017997:Leukotriene C4; D017998:Leukotriene D4; D017999:Leukotriene E4; C412375:cysteinyl leukotriene receptor 2; D003545:Cysteine