Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 275 (52), 40686-94

A Novel Hepatointestinal Leukotriene B4 Receptor. Cloning and Functional Characterization

Affiliations

A Novel Hepatointestinal Leukotriene B4 Receptor. Cloning and Functional Characterization

S Wang et al. J Biol Chem.

Abstract

Leukotriene B(4) (LTB(4)) is a product of eicosanoid metabolism and acts as an extremely potent chemotactic mediator for inflammation. LTB(4) exerts positive effects on the immigration and activation of leukocytes. These effects suggest an involvement of LTB(4) in several diseases: inflammatory bowel disease, psoriasis, arthritis, and asthma. LTB(4) elicits actions through interaction with one or more cell surface receptors that lead to chemotaxis and inflammation. One leukotriene B(4) receptor has been recently identified (LTB(4)-R1). In this report we describe cloning of a cDNA encoding a novel 358-amino acid receptor (LTB(4)-R2) that possesses seven membrane-spanning domains and is homologous (42%) and genetically linked to LTB(4)-R1. Expression of LTB(4)-R2 is broad but highest in liver, intestine, spleen, and kidney. In radioligand binding assays, membranes prepared from COS-7 cells transfected with LTB(4)-R2 cDNA displayed high affinity (K(d) = 0.17 nm) for [(3)H]LTB(4). Radioligand competition assays revealed high affinities of the receptor for LTB(4) and LTB(5), and 20-hydroxy-LTB(4), and intermediate affinities for 15(S)-HETE and 12-oxo-ETE. Three LTB(4) receptor antagonists, 14,15-dehydro-LTB(4), LTB(4)-3-aminopropylamide, and U-75302, had high affinity for LTB(4)-R1 but not for LTB(4)-R2. No apparent affinity binding for the receptors was detected for the CysLT1-selective antagonists montelukast and zafirlukast. LTB(4) functionally mobilized intracellular calcium and inhibited forskolin-stimulated cAMP production in 293 cells. The discovery of this new receptor should aid in further understanding the roles of LTB(4) in pathologies in these tissues and may provide a tool in identification of specific antagonists/agonists for potential therapeutic treatments.

Similar articles

  • cDNA Cloning and Characterization of Guinea-Pig Leukotriene B4 Receptor
    K Masuda et al. Biochem J 342 ( Pt 1) (Pt 1), 79-85. PMID 10432303.
    The cDNA for leukotriene B(4) (LTB(4)) receptor (BLT) was cloned from a guinea-pig leucocyte cDNA library. The cloned receptor cDNA encodes 348 amino acid residues and sh …
  • A G-protein-coupled Receptor for Leukotriene B4 That Mediates Chemotaxis
    T Yokomizo et al. Nature 387 (6633), 620-4. PMID 9177352.
    Leukotriene B4 (LTB4) is a potent chemoattractant that is primarily involved in inflammation, immune responses and host defence against infection. LTB4 activates inflamma …
  • Cloning and Characterization of Rat Leukotriene B(4) Receptor
    A Toda et al. Biochem Biophys Res Commun 262 (3), 806-12. PMID 10471406.
    Leukotriene B(4) (LTB(4)) is a potent chemoattractant for neutrophils and eosinophils. cDNAs for LTB(4) receptor (BLT) have been cloned from human, mouse, and guinea pig. …
  • BLT1 and BLT2: The Leukotriene B(4) Receptors
    AM Tager et al. Prostaglandins Leukot Essent Fatty Acids 69 (2-3), 123-34. PMID 12895595. - Review
    Two receptors for leukotriene B(4) (LTB(4)) have been molecularly identified: BLT1 and BLT2. Both receptors are G protein-coupled seven transmembrane domain receptors, wh …
  • Leukotriene B4 Receptor and the Function of Its Helix 8
    T Okuno et al. J Biol Chem 280 (37), 32049-52. PMID 16046389. - Review
    More than 30 lipid ligands, which express their biological activities through cognate G-protein-coupled receptors (GPCRs), have been reported. Among them, leukotriene B(4 …
See all similar articles

Cited by 7 PubMed Central articles

See all "Cited by" articles

Associated data

LinkOut - more resources

Feedback