title: Cysteinyl leukotriene receptor 1 is also a pyrimidinergic receptor and is expressed by human mast cells.
abstract: The cysteinyl leukotrienes (cys-LTs) LTC(4), LTD(4), and LTE(4) are a class of peptide-conjugated lipids formed from arachidonic acid and released during activation of mast cells (MCs). We now report that human cord-blood-derived MCs (hMCs) express the CysLT1 receptor, which responds not only to inflammation-derived cys-LTs, but also to a pyrimidinergic ligand, UDP. hMCs express both CysLT1 protein and transcript, and respond to LTC(4), LTD(4), and UDP with concentration-dependent calcium fluxes, each of which is blocked by a competitive CysLT1 receptor antagonist, MK571. Stably transfected Chinese hamster ovary cells expressing the CysLT1 receptor also exhibit MK571-sensitive calcium flux to all three agonists. Both hMCs and CysLT1 transfectants stimulated with UDP are desensitized to LTC(4), but only partially to LTD(4). Priming of hMCs with IL-4 for 5 days enhances their sensitivity to each agonist, but preferentially lowers their threshold for activation by LTC(4) and UDP (approximately 3 log(10)-fold shifts in dose-response for each agonist) over LTD(4) (1.3 log(10)-fold shift), without altering CysLT1 receptor mRNA or surface protein expression, implying the likely induction of a second receptor with CysLT1-like dual ligand specificity. hMCs thus express the CysLT1 receptor, and possibly a closely related IL-4-inducible receptor, which mediate dual activation responses to cys-LTs and UDP, providing an apparent intersection linking the inflammatory and neurogenic elements of bronchial asthma.
authors: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: E A
authors: EA
authors: Mellor
authors: A
authors: A
authors: Maekawa
authors: K F
authors: KF
authors: Austen
authors: J A
authors: JA
authors: Boyce
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008407:Mast Cells / Q000276:immunology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011422:Propionates / Q000494:pharmacology; D011743:Pyrimidines / Q000276:immunology*; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018077:Receptors, Leukotriene / Q000276:immunology*; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011422:Propionates; D011743:Pyrimidines; D011804:Quinolines; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; C059141:verlukast; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor