School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
Mol Pharmacol. 2013 Feb;83(2):389-98. doi: 10.1124/mol.112.081315. Epub 2012 Nov 15.
The evolutionary relationship and functional correlation between human formyl peptide receptors (FPRs) and their mouse counterparts remain incompletely understood. We examined three members of the mouse formyl peptide receptor subfamily (mFprs) and found that they differ in agonist preference and cellular distributions. When stably expressed in transfected rat basophilic leukemia (RBL-2H3) cells, mFpr1 was readily activated by N-formylated peptides derived from Listeria monocytogenes (fMIVTLF), Staphylococcus aureus (fMIFL), and mitochondria (fMMYALF). In contrast, the Escherichia coli-derived fMLF was 1000-fold less potent. The aforementioned peptides were much less efficacious at mFpr2, which responded better to the synthetic hexapeptide WKYMVm, the synthetic agonists Quin-C1 (a substituted quinazolinone), and compound 43 (a nitrosylated pyrazolone derivative). Saturation binding assays showed that mFpr1 and mFpr2 were expressed at similar levels on the cell surface, although their affinity for N-formyl-Met-Leu-Phe-Ile-Ile-Lys-fluorescein isothiocyanate varied by more than 1000-fold [dissociation constant (K(d)) values of 2.8 nM for mFpr1 and 4.8 μM for mFpr2]). Contrary to these receptors, mFpr-rs1 responded poorly to all the previously mentioned peptides that were tested. Fluorescent microscopy revealed an intracellular distribution pattern of mFpr-rs1. On the basis of these results, we conclude that mFpr1 is an ortholog of human FPR1 with certain pharmacologic properties of human FPR2/ALX, whereas mFpr2 has much lower affinity for formyl peptides. The intracellular distribution of mFpr-rs1 suggests an evolutionary correlation with human FPR3.
人类形式肽受体（FPRs）与其小鼠对应物之间的进化关系和功能相关性仍不完全清楚。我们研究了小鼠形式肽受体亚家族的三个成员（mFprs），发现它们在激动剂偏好和细胞分布上存在差异。当稳定表达在转染的大鼠嗜碱性白血病（RBL-2H3）细胞中时，mFpr1 很容易被来自李斯特菌（fMIVTLF）、金黄色葡萄球菌（fMIFL）和线粒体（fMMYALF）的 N-甲酰肽激活。相比之下，大肠杆菌来源的 fMLF 效力低 1000 倍。上述肽类物质在 mFpr2 中的效力要低得多，mFpr2 对合成六肽 WKYMVm、合成激动剂 Quin-C1（取代的喹唑啉酮）和化合物 43（硝化吡唑酮衍生物）反应更好。饱和结合测定表明，mFpr1 和 mFpr2 在细胞表面的表达水平相似，尽管它们对 N-甲酰-Met-Leu-Phe-Ile-Ile-Lys-荧光素异硫氰酸酯的亲和力差异超过 1000 倍[mFpr1 的解离常数（K(d)值为 2.8 nM，mFpr2 的 K(d)值为 4.8 μM)]。与这些受体相反，mFpr-rs1 对所有测试的上述肽类物质反应不佳。荧光显微镜显示 mFpr-rs1 的细胞内分布模式。基于这些结果，我们得出结论，mFpr1 是人类 FPR1 的同源物，具有人类 FPR2/ALX 的某些药理学特性，而 mFpr2 对形式肽的亲和力较低。mFpr-rs1 的细胞内分布表明与人类 FPR3 存在进化相关性。
