The murine cysteinyl leukotriene 2 (CysLT2) receptor: cDNA and genomic cloning, alternative splicing, and in vitro characterization

Yiqun Hui, Guochang Yang, Helen Galczenski, David J. Figueroa, Christopher P. Austin, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Colin D. Funk

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Two classes of cysteinyl leukotriene receptor, CysLT1 and CysLT2, have been identified and pharmacologically characterized in human tissues. Although the CysLT1 receptor mediates the proinflammatory effects of leukotrienes in human asthma, the physiological roles of CysLT2 receptor are not defined, and a suitable mouse model would be useful in delineating function. We report here the molecular cloning and characterization of the mouse CysLT2 receptor (mCysLT2R) from heart tissue. mCysLT2R cDNA encodes a protein of 309 amino acids, truncated at both ends compared with the human ortholog (hCysLT2R). The gene resides on the central region of mouse chromosome 14 and is composed of 6 exons with the entire coding region located in the last exon. Two 5′-untranslated region splice variants were identified with the short form lacking exon 3 as the predominant transcript. Although the overall expression of mCysLT2R is very low, the highest expression was detected in spleen, thymus, and adrenal gland by ribonuclease protection assay, and discrete sites of expression in heart were observed by in situ hybridization. Intracellular calcium mobilization in response to cysteinyl leukotriene administration was detected in human embryonic kidney 293T cells transfected with recombinant mCysLT2R with a rank order of potency leukotriene C4 (LTC4) = LTD4 ≫ LTE4. [ 3H]LTD4 binding to membranes expressing mCysLT 2R could be effectively competed by LTC4 and LTD 4 and only partially inhibited by LTE4 and BAYu9773. The identification of mCysLT2R will be useful for establishing CysLT 2R-deficient mice and determining novel leukotriene functions.

Original languageEnglish (US)
Pages (from-to)47489-47495
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number50
DOIs
StatePublished - Dec 14 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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