These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT₂) agonist, N-methyl-leukotriene C₄, in calcium reporter and β arrestin assays.
    Author: Yan D, Stocco R, Sawyer N, Nesheim ME, Abramovitz M, Funk CD.
    Journal: Mol Pharmacol; 2011 Feb; 79(2):270-8. PubMed ID: 21078884.
    Abstract:
    The cysteinyl leukotrienes (cysLTs) LTC₄, LTD₄, and LTE₄ are lipid mediators with physiological and pathophysiological functions. They exert their effects through G protein-coupled receptors (GPCRs), most notably via CysLT₁ and CysLT₂ receptor. The roles of the CysLT₂ receptor are beginning to emerge. Both LTC₄ and LTD₄ are potent agonists for the CysLT₂ receptor; however, LTC₄ is rapidly converted to LTD₄, which is also the main endogenous ligand for the CysLT₁ receptor. A selective and potent agonist at the CysLT₂ receptor would facilitate studies to discern between receptor subtypes. We show here that N-methyl LTC₄ (NMLTC₄), a metabolically stable LTC₄ mimetic, is a potent and selective CysLT₂ receptor agonist. Two expression systems were used to evaluate the functional activity of NMLTC₄ at human and/or mouse CysLT₁ and CysLT₂ receptors. Through the aequorin cell-based assay for calcium-coupled GPCRs, NMLTC₄ was almost equipotent to LTC₄ at CysLT₂ receptors but was the least efficacious at CysLT₂ receptors. In a β-galactosidase-β-arrestin complementation assay, the human (h) CysLT₂ receptor can couple with β-arrestin-2, and NMLTC₄ is slightly more potent for eliciting β-arrestin-2 binding compared with cysLTs. Furthermore, LTE₄ is nearly inactive in this assay compared with its weak partial agonist activity in the aequorin system. In a vascular leakage assay, NMLTC₄ is potent and active in mice overexpressing hCysLT₂ receptor in endothelium, whereas the response is abrogated in CysLT₂ receptor knockout mice. Therefore, NMLTC₄ is a potent subtype selective agonist for the CysLT₂ receptor in vitro and in vivo, and it will be useful to elucidate its biological roles.
    [Abstract] [Full Text] [Related] [New Search]