Abstract:
The Ca2+-sensing receptor (CaSR) is a G-protein-coupled receptor activated by elevated concentrations of extracellular Ca2+, and was initially known for its regulation of parathyroid hormone (PTH) release. Ubiquitous expression of CaSR in different tissues and organs was later noted and CaSR participation in various physiological functions was demonstrated. Accumulating evidence has suggested that CaSR functionally interacts with transient receptor potential (TRP) channels, which are mostly non-selective cation channels involved in sensing temperature, pain and stress. This review describes the interactions of CaSR with TRP channels in diverse cell types to trigger a variety of biological responses. CaSR has been known to interact with different types of G proteins. Possible involvements of G proteins, other signaling and scaffolding protein intermediates in CaSR-TRP interaction are discussed. In addition, an attempt will be made to extend the current understanding of biased agonism of CaSR.
摘要:
Ca2+敏感受体(CaSR)是一种G-蛋白偶联受体,由细胞外Ca2+浓度升高激活,最初以调节甲状旁腺激素(PTH)释放而闻名。后来注意到CaSR在不同组织和器官中的普遍表达,并证明了CaSR参与各种生理功能。越来越多的证据表明,CaSR在功能上与瞬时受体电位(TRP)通道相互作用,它们大多是参与感知温度的非选择性阳离子通道,疼痛和压力。这篇综述描述了CaSR与不同细胞类型中TRP通道的相互作用,以触发多种生物反应。已知CaSR与不同类型的G蛋白相互作用。可能涉及G蛋白,讨论了CaSR-TRP相互作用中的其他信号和支架蛋白中间体。此外,将尝试扩展对CaSR的偏见激动的当前理解。