Umeda Tatsuya, Kanatani Akio, Iwaasa Hisashi
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan.
Peptides. 2009 Aug;30(8):1441-7. doi: 10.1016/j.peptides.2009.05.020. Epub 2009 May 27.
Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are structurally related peptides that have numerous functions in both neural and endocrine signaling. These effects are mediated by the NPY receptor family and five members of this family have been cloned in mammals. To better characterize these receptor subtypes, we cloned and expressed the Y1, Y2, Y4 and Y5 receptor subtypes from the rabbit. Comparison of these sequences with human orthologs revealed that the Y1, Y2 and Y5 receptors have generally strong amino-acid sequence conservation, with 91-96% identity, while Y4 receptor showed relatively weak similarity with 82% identity, as with other species. Particularly in the transmembrane regions, Y1, Y2, and Y5 receptor subtypes showed remarkable conservation, with 98-99% amino acid identity. Competitive binding studies by NPY-family peptides and analogs showed that Y1, Y2 and Y5 receptors had similar pharmacological profiles between the respective rabbit and human receptor subtypes. Interestingly, all the tested peptides had a greater affinity for rabbit Y4 receptor than human Y4 receptor. These results suggest that rabbit and human Y1, Y2 and Y5 receptor subtypes are well conserved, whereas Y4 receptors are less well conserved.
神经肽Y（NPY）、肽YY（PYY）和胰多肽（PP）是结构相关的肽类，在神经和内分泌信号传导中具有多种功能。这些作用由NPY受体家族介导，该家族的五个成员已在哺乳动物中克隆出来。为了更好地表征这些受体亚型，我们从兔中克隆并表达了Y1、Y2、Y4和Y5受体亚型。将这些序列与人类直系同源物进行比较发现，Y1、Y2和Y5受体通常具有很强的氨基酸序列保守性，同一性为91 - 96%，而Y4受体与其他物种一样，显示出相对较弱的相似性，同一性为82%。特别是在跨膜区域，Y1、Y2和Y5受体亚型显示出显著的保守性，氨基酸同一性为98 - 99%。NPY家族肽和类似物的竞争性结合研究表明，Y1、Y2和Y5受体在各自的兔和人类受体亚型之间具有相似的药理学特征。有趣的是，所有测试的肽对兔Y4受体的亲和力都比对人类Y4受体的亲和力更高。这些结果表明，兔和人类的Y1、Y2和Y5受体亚型保守性良好，而Y4受体的保守性较差。
