PT  - JOURNAL ARTICLE
AU  - Henry M. Sarau
AU  - Robert S. Ames
AU  - Jon Chambers
AU  - Catherine Ellis
AU  - Nabil Elshourbagy
AU  - James J. Foley
AU  - Dulcie B. Schmidt
AU  - Roseanna M. Muccitelli
AU  - Owen Jenkins
AU  - Paul R. Murdock
AU  - Nicole C. Herrity
AU  - Wendy Halsey
AU  - Ganesh Sathe
AU  - Alison I. Muir
AU  - Parvathi Nuthulaganti
AU  - George M. Dytko
AU  - Peter T. Buckley
AU  - Shelagh Wilson
AU  - Derk J. Bergsma
AU  - Douglas W.P. Hay
TI  - Identification, Molecular Cloning, Expression, and Characterization of a Cysteinyl Leukotriene Receptor
AID  - 10.1124/mol.56.3.657
DP  - 1999 Sep 01
TA  - Molecular Pharmacology
PG  - 657--663
VI  - 56
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/56/3/657.short
4100  - http://molpharm.aspetjournals.org/content/56/3/657.full
SO  - Mol Pharmacol1999 Sep 01; 56
AB  - The cysteinyl leukotrienes (CysLTs) have been implicated in the pathophysiology of inflammatory disorders, in particular asthma, for which the CysLT receptor antagonists pranlukast, zafirlukast, and montelukast, have been introduced recently as novel therapeutics. Here we report on the molecular cloning, expression, localization, and pharmacological characterization of a CysLT receptor (CysLTR), which was identified by ligand fishing of orphan seven-transmembrane-spanning, G protein-coupled receptors. This receptor, expressed in human embryonic kidney (HEK)-293 cells responded selectively to the individual CysLTs, LTC4, LTD4, or LTE4, with a calcium mobilization response; the rank order potency was LTD4(EC50 = 2.5 nM) > LTC4(EC50 = 24 nM) > LTE4(EC50 = 240 nM). Evidence was provided that LTE4 is a partial agonist at this receptor. [3H]LTD4 binding and LTD4-induced calcium mobilization in HEK-293 cells expressing the CysLT receptor were potently inhibited by the structurally distinct CysLTR antagonists pranlukast, montelukast, zafirlukast, and pobilukast; the rank order potency was pranlukast = zafirlukast > montelukast > pobilukast. LTD4-induced calcium mobilization in HEK-293 cells expressing the CysLT receptor was not affected by pertussis toxin, and the signal appears to be the result of the release from intracellular stores. Localization studies indicate the expression of this receptor in several tissues, including human lung, human bronchus, and human peripheral blood leukocytes. The discovery of this receptor, which has characteristics of the purported CysLT1 receptor subtype, should assist in the elucidation of the pathophysiological roles of the CysLTs and in the identification of additional receptor subtypes.