Cysteinyl leukotriene receptors
Cysteinyl leukotriene receptors
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DOI：
10.1016/s0090-6980(02)00057-6
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发表时间：
2002-08-01
影响因子：
2.9
通讯作者：
Evans, JF
中科院分区：
文献类型：
--
作者：
Evans, JF
半胱氨酸白三烯、白三烯C-4 （LTC4）、白三烯D-4 （LTD4）和白三烯E-4 （LTE4）通过与7种跨膜受体的特异性相互作用激活收缩和炎症过程，这些受体与G蛋白偶联并随后进入细胞内信号通路。基于生物反应的激动剂和拮抗剂效力，药理学特征确定了至少两种半胱氨酸白三烯（CysLT）受体亚型。CysLT(1)受体激动剂激活的等级效价为LTD4 > LTC4 > LTE4, CysLT(2)受体激动剂激活的等级效价为LTC4 = LTD4 > LTE4。CysLT(1)选择性受体拮抗剂是治疗哮喘的有效药物。没有选择性的CysLT(2)受体拮抗剂被描述。人和小鼠CysLT(1)和CysLT(2)受体的分子鉴定证实了它们的结构是假定的7个跨膜结构域G蛋白偶联受体，并在很大程度上证实了先前的药理学表征。CysLT(1)受体在脾脏、包括嗜酸性粒细胞在内的外周血白细胞、肺平滑肌细胞和肺间质巨噬细胞中表达量最高。CysLT(2)受体在心脏、肾上腺髓质、胎盘和外周血白细胞中表达量最高。小鼠CysLT(1)和CysLT(2)受体的分子鉴定显示出与人类同源受体相似但不完全相同的特征。(C) 2002爱思唯尔科学有限公司版权所有。
The cysteinyl leukotrienes, leukotriene C-4 (LTC4), leukotriene D-4 (LTD4) and leukotriene E-4 (LTE4), activate contractile and inflammatory processes via specific interaction with putative seven transmembrane-spanning receptors that couple to G proteins and subsequent intracellular signaling pathways. Pharmacological characterizations identified at least two subtypes of cysteinyl leukotriene (CysLT) receptor based on agonist and antagonist potency for biological responses. The rank potency of agonist activation for the CysLT(1) receptor is LTD4 > LTC4 > LTE4 and for the CysLT(2) receptor is LTC4 = LTD4 > LTE4. CysLT(1) selective receptor antagonists are efficacious in the treatment of asthma. No selective CysLT(2) receptor antagonists have been described. Molecular identification of the human and mouse CysLT(1) and CysLT(2) receptors has confirmed their structure as putative seven transmembrane domain G protein-coupled receptors and largely confirmed the previous pharmacological characterizations. The CysLT(1) receptor is most highly expressed in spleen, peripheral blood leukocytes including eosinophils, and lung smooth muscle cells and interstitial lung macrophages. The CysLT(2) receptor is most highly expressed in the heart, adrenal medulla, placenta and peripheral blood leukocytes. The molecular identification of the mouse CysLT(1) and CysLT(2) receptors show similar but not identical profiles to the orthologous human receptors. (C) 2002 Elsevier Science Inc. All rights reserved.