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  • Title: Dominant expression of the CysLT2 receptor accounts for calcium signaling by cysteinyl leukotrienes in human umbilical vein endothelial cells.
    Author: Sjöström M, Johansson AS, Schröder O, Qiu H, Palmblad J, Haeggström JZ.
    Journal: Arterioscler Thromb Vasc Biol; 2003 Aug 01; 23(8):e37-41. PubMed ID: 12816881.
    Abstract:
    OBJECTIVE: The objective of the present study was to identify and characterize the cell-surface receptors on human umbilical vein endothelial cells (HUVECs) that transduce calcium transients elicited by cysteinyl leukotrienes (CysLTs), potent spasmogenic and proinflammatory agents with profound effects on the cardiovascular system. METHODS AND RESULTS: Using quantitative reverse transcription-polymerase chain reaction, we found that HUVECs abundantly express CysLT2R mRNA in vast excess (>4000-fold) of CysLT1R mRNA. Lipopolysaccharide, tumor necrosis factor-alpha, or interleukin-1beta caused a rapid (within 30 minutes) and partially reversible suppression of CysLT2R mRNA levels. Challenge of HUVECs with BAY u9773, a specific CysLT2R agonist, triggered diagnostic Ca2+ transients. LTC4 and LTD4 are equipotent agonists, and their actions can be blocked by the dual-receptor antagonist BAY u9773, but not by the CysLT1R-selective antagonist MK571. CONCLUSIONS: HUVECs almost exclusively express the CysLT2R. Furthermore, Ca2+ fluxes elicited by CysLT in these cells emanate from perturbation of the CysLT2R, rather than the expected CysLT1R. Hence, signaling events involving CysLT2R might trigger functional responses involved in the critical components of LT-dependent vascular reactions, which in turn have implications for ischemic heart disease and myocardial infarction.
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