Larsson Tomas A, Larson Earl T, Fredriksson Robert, Conlon J Michael, Larhammar Dan
Department of Neuroscience, Uppsala University, Box 593, SE-75124, Uppsala, Sweden.
Peptides. 2006 Jun;27(6):1320-7. doi: 10.1016/j.peptides.2005.10.008. Epub 2005 Dec 15.
We report the cloning and pharmacological characterization of two neuropeptide Y (NPY) receptor subtypes, Y2 and Y7, in rainbow trout (Oncorhynchus mykiss). These subtypes are approximately 50% identical to each other and belong to the Y2 subfamily of NPY receptors. The binding properties of the receptors were investigated after expression in human HEK-293 EBNA cells. Both receptors bound the three zebrafish peptides NPY, PYYa, and PYYb, as well as porcine NPY and PYY, with affinities in the nanomolar range that are similar to mammalian Y2. The affinity of the truncated porcine NPY fragments, NPY 13-36 and NPY 18-36 was markedly lower compared to mammalian and chicken Y2. This suggests that mammalian and chicken Y2 are unique among NPY receptors in their ability to bind truncated peptide fragments. The antagonist BIIE0246, developed for mammalian Y2, did not bind either of the two rainbow trout receptors. Our results support the proposed expansion of this gene family by duplications before the gnathostome radiation. They also reveal appreciable differences in the repertoire and characteristics of NPY receptors between fish and tetrapods stressing the importance of lineage-specific gene loss as well as sequence divergence after duplication.
我们报道了虹鳟（Oncorhynchus mykiss）中两种神经肽Y（NPY）受体亚型Y2和Y7的克隆及药理学特性。这些亚型彼此间约有50%的同源性，属于NPY受体的Y2亚家族。在人HEK-293 EBNA细胞中表达后，研究了这些受体的结合特性。两种受体均能结合三种斑马鱼肽NPY、PYYa和PYYb，以及猪NPY和PYY，亲和力在纳摩尔范围内，与哺乳动物Y2相似。与哺乳动物和鸡的Y2相比，截短的猪NPY片段NPY 13 - 36和NPY 18 - 36的亲和力明显较低。这表明哺乳动物和鸡的Y2在结合截短肽片段的能力方面在NPY受体中是独特的。为哺乳动物Y2开发的拮抗剂BIIE0246不与两种虹鳟受体中的任何一种结合。我们的结果支持了在有颌类辐射之前通过基因复制导致该基因家族扩张的观点。它们还揭示了鱼类和四足动物之间NPY受体的种类和特性存在明显差异，强调了谱系特异性基因丢失以及复制后序列分歧的重要性。
