Pharmacological characterization of relaxin-3/INSL7 receptors GPCR135 and GPCR142 from different mammalian species
Pharmacological characterization of relaxin-3/INSL7 receptors GPCR135 and GPCR142 from different mammalian species
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DOI：
10.1124/jpet.104.073486
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发表时间：
2005-01-01
影响因子：
3.5
通讯作者：
Liu, CL
中科院分区：
文献类型：
--
作者：
Chen, JC;Kuei, C;Liu, CL
松弛素-3最近被鉴定为两种结构相关的G蛋白偶联受体（人GPCR 135和GPCR 142）的配体。本研究报告了小鼠和大鼠GPCR 135以及来自小鼠、猴、牛和猪的GPCR 142在分子和药理学水平的表征。小鼠和大鼠GPCR 135与人GPCR 135具有高度同源性（>85%），并且具有与人GPCR 135非常相似的药理学性质。人和小鼠/大鼠松弛素-3均以接近0.5 nM的IC 50或EC 50值高亲和力结合并激活小鼠、大鼠和人GPCR 135。相比之下，小鼠GPCR 142与人GPCR 142的保守性较低（74%同源性）。大鼠GPCR 142基因为假基因。我们进一步从猴、牛和猪中克隆了GPCR 142基因，发现它们与人GPCR 142高度同源（>84%）。不同物种的GPCR 142的药理学表征表明松弛素-3以高亲和力（IC 50）结合不同物种的GPCR 142
Relaxin-3 has recently been identified as a ligand for two structurally related G-protein-coupled receptors, human GPCR135 and GPCR142. This current study reports the characterization of mouse and rat GPCR135 as well as GPCR142 from mouse, monkey, cow, and pig at the molecular and pharmacological levels. Mouse and rat GPCR135 exhibit high homology (>85%) to the human GPCR135 and have very similar pharmacological properties to that of the human GPCR135. Human and mouse/rat relaxin-3 both bind to and activate mouse, rat, and human GPCR135 at high affinity with IC50 or EC50 values close to 0.5 nM. In contrast, the mouse GPCR142 is less well conserved (74% homology) with human GPCR142. The rat GPCR142 gene was found to be a pseudogene. We further cloned GPCR142 genes from monkey, cow, and pig and found that they are highly homologous (>84%) to human GPCR142. Pharmacological characterization of GPCR142 from different species demonstrated that relaxin-3 binds to GPCR142 from different species at high affinity (IC50