Identification, Molecular Cloning, Expression, and Characterization of a Cysteinyl Leukotriene Receptor
| العنوان: | Identification, Molecular Cloning, Expression, and Characterization of a Cysteinyl Leukotriene Receptor |
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| المؤلفون: | Peter T. Buckley, Paul R. Murdock, Catherine E. Ellis, Nabil Elshourbagy, Owen Jenkins, Douglas W. P. Hay, Nicole C. Herrity, Ganesh M. Sathe, James J. Foley, Alison I. Muir, Parvathi Nuthulaganti, Jon K. Chambers, Shelagh Wilson, Roseanna M. Muccitelli, George M. Dytko, Wendy S. Halsey, Dulcie B. Schmidt, Henry M. Sarau, Derk J. Bergsma, Robert S. Ames |
| المصدر: | Molecular Pharmacology. 56:657-663 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Molecular Sequence Data, Biology, Pharmacology, Pranlukast, Leukotriene D4, medicine, Enzyme-linked receptor, Humans, 5-HT5A receptor, Amino Acid Sequence, Virulence Factors, Bordetella, Cloning, Molecular, Zafirlukast, Receptor, Cells, Cultured, Receptors, Leukotriene, Binding Sites, Base Sequence, Membrane Proteins, Biological Transport, respiratory system, Cysteinyl leukotriene receptor 1, Cysteinyl leukotriene receptor 2, Pertussis Toxin, Interleukin-21 receptor, Molecular Medicine, Calcium, lipids (amino acids, peptides, and proteins), Signal Transduction, medicine.drug |
| الوصف: | 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, LTC(4), LTD(4), or LTE(4), with a calcium mobilization response; the rank order potency was LTD(4) (EC(50) = 2.5 nM)LTC(4) (EC(50) = 24 nM)LTE(4) (EC(50) = 240 nM). Evidence was provided that LTE(4) is a partial agonist at this receptor. [(3)H]LTD(4) binding and LTD(4)-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 = zafirlukastmontelukastpobilukast. LTD(4)-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 CysLT(1) receptor subtype, should assist in the elucidation of the pathophysiological roles of the CysLTs and in the identification of additional receptor subtypes. |
| تدمد: | 1521-0111 0026-895X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7b162a4b722162fccd8a0083f840edb https://doi.org/10.1124/mol.56.3.657 |
| رقم الأكسشن: | edsair.doi.dedup.....d7b162a4b722162fccd8a0083f840edb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210111 0026895X |
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