Capra Valérie, Thompson Miles D, Sala Angelo, Cole David E, Folco Giancarlo, Rovati G Enrico
Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Med Res Rev. 2007 Jul;27(4):469-527. doi: 10.1002/med.20071.
Cysteinyl-leukotrienes (cysteinyl-LTs), that is, LTC4, LTD4, and LTE4, trigger contractile and inflammatory responses through the specific interaction with G protein-coupled receptors (GPCRs) belonging to the purine receptor cluster of the rhodopsin family, and identified as CysLT receptors (CysLTRs). Cysteinyl-LTs have a clear role in pathophysiological conditions such as asthma and allergic rhinitis (AR), and have been implicated in other inflammatory conditions including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. Molecular cloning of human CysLT1R and CysLT2R subtypes has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Interestingly, recent data provide evidence for the immunomodulation of CysLTR expression, the existence of additional receptor subtypes, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Furthermore, genetic variants have been identified for the CysLTRs that may interact to confer risk for atopy. Finally, a crosstalk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize and attempt to integrate recent data derived from studies on the molecular pharmacology and pharmacogenetics of CysLTRs, and will consider the therapeutic opportunities arising from the new roles suggested for cysteinyl-LTs and their receptors.
半胱氨酰白三烯（cysteinyl-LTs），即LTC4、LTD4和LTE4，通过与视紫红质家族嘌呤受体簇中的G蛋白偶联受体（GPCRs）特异性相互作用引发收缩和炎症反应，这些受体被鉴定为半胱氨酰白三烯受体（CysLTRs）。半胱氨酰白三烯在诸如哮喘和变应性鼻炎（AR）等病理生理状况中具有明确作用，并且还与包括心血管疾病、癌症、特应性皮炎和荨麻疹在内的其他炎症状况有关。人CysLT1R和CysLT2R亚型的分子克隆证实了先前的大部分药理学特征，并确定了仅部分重叠的不同表达模式。有趣的是，最近的数据为CysLTR表达的免疫调节、额外受体亚型的存在以及可能具有与质膜受体不同作用的CysLTRs细胞内池提供了证据。此外，已经确定了CysLTRs的基因变体，这些变体可能相互作用以赋予患特应性疾病的风险。最后，半胱氨酰白三烯与嘌呤系统之间的串扰正在被阐明。本综述将总结并尝试整合来自CysLTRs分子药理学和药物遗传学研究的最新数据，并将考虑由半胱氨酰白三烯及其受体的新作用所带来的治疗机会。
