IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F35/2023.1

Leukotriene receptors in GtoPdb v.2023.1



Magnus Bäck1, Charles Brink2, Nan Chiang3, Sven-Erik Dahlén1, Gordon Dent4, Jeffrey Drazen5, Jilly F. Evans6, Douglas W. P. Hay7, Motonao Nakamura8, William Powell9, Joshua Rokach10, G. Enrico Rovati11, Charles N. Serhan5, Takao Shimizu8, Mohib Uddin12 and Takehiko Yokomizo13
  1. Karolinska Institutet, Sweden
  2. Hopital Marie Lannelongue, France
  3. Brigham and Women's Hospital, USA
  4. Keele University, UK
  5. Harvard University, USA
  6. PharmAkea, USA
  7. GlaxoSmithKline, USA
  8. University of Tokyo, Japan
  9. McGill University, Canada
  10. Florida Institute of Technology, USA
  11. University of Milan, Italy
  12. AstraZeneca, Sweden
  13. Juntendo University, Japan


Abstract

The leukotriene receptors (nomenclature as agreed by the NC-IUPHAR subcommittee on Leukotriene Receptors [35, 38]) are activated by the endogenous ligands leukotrienes (LT), synthesized from lipoxygenase metabolism of arachidonic acid. The human BLT1 receptor is the high affinity LTB4 receptor whereas the BLT2 receptor in addition to being a low-affinity LTB4 receptor also binds several other lipoxygenase-products, such as 12S-HETE, 12S-HPETE, 15S-HETE, and the thromboxane synthase product 12-hydroxyheptadecatrienoic acid. The BLT receptors mediate chemotaxis and immunomodulation in several leukocyte populations and are in addition expressed on non-myeloid cells, such as vascular smooth muscle and endothelial cells. In addition to BLT receptors, LTB4 has been reported to bind to the peroxisome proliferator activated receptor (PPAR) α [201] and the vanilloid TRPV1 ligand-gated nonselective cation channel [223]. The crystal structure of the BLT1 receptor was initially determined in complex with selective antagonists [141, 231] and has recently been extended to the cryo-electron microscopy structure of LTB4-bound human BLT1 receptor at 2.91 Å resolution [389]. The receptors for the cysteinyl-leukotrienes (i.e. LTC4, LTD4 and LTE4) are termed CysLT1 and CysLT2 and exhibit distinct expression patterns in human tissues, mediating for example smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation. Quite recently, the the crystal structures of both receptors have been solved, the CysLT1 in complex with zafirlukast and pranlukast [203] and the CysLT2 in complex with three dual CysLT1/CysLT2 antagonists [122]. There is also evidence in the literature for additional CysLT receptor subtypes, derived from functional in vitro studies, radioligand binding and in mice lacking both CysLT1 and CysLT2 receptors [38]. Cysteinyl-leukotrienes have also been suggested to signal through the P2Y12 receptor [99, 251, 280], GPR17 [60] and GPR99 [173].

Contents

This is a citation summary for Leukotriene receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts. For further details see [33].

Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.

Database links

Leukotriene receptors
https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=35
Introduction to Leukotriene receptors
https://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=35
    Receptors
            BLT1 receptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=267
            BLT2 receptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=268
            CysLT1 receptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=269
            CysLT2 receptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=270
            OXE receptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=271
            FPR2/ALX
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=223

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