Pharmacological characterization of cloned chicken neuropeptide Y receptors Y1 and Y5
Pharmacological characterization of cloned chicken neuropeptide Y receptors Y1 and Y5
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DOI：
10.1046/j.1471-4159.2002.00817.x
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发表时间：
2002-05-01
影响因子：
4.7
通讯作者：
Larhammar, D
中科院分区：
文献类型：
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作者：
Holmberg, SKS;Mikko, S;Larhammar, D
神经肽Y(NPY)受体亚型Y-1和Y-5参与哺乳动物的摄食调节和其他几种生理功能。为了加深我们对NPY复杂系统的起源和机制的了解，我们报道了第一个非哺乳动物鸡(Gallus Gallus)Y-1和Y-5受体的克隆和药理特性。这些受体与其哺乳动物同源物的氨基酸序列同源性分别为80%~83%和72%。三种内源性配体NPY、PYY(PYY)和胰多肽(PP)与哺乳动物具有相似的亲和力，即NPY和PYY对这两种受体具有亚纳摩尔亲和力，而鸡PP与Y-5结合纳摩尔亲和力，而与Y-1不结合。与哺乳动物受体亚型显著不同的是，Y-1拮抗剂SR120819A不与鸡Y-1结合，而BIBP3226则与Y-5受体结合，Y-5拮抗剂CGP71863A与鸡Y-5受体结合。在解剖学上，Y-1和Y-5在哺乳动物下丘脑弓状核的同源结构漏斗核中都有高水平的mRNA表达。这些结果表明，在哺乳动物中开发的一些选择性Y-1和Y-5拮抗剂可以用于研究鸡的食欲调节。
The neuropeptide Y (NPY) receptor subtypes Y-1 and Y-5 are involved in the regulation of feeding and several other physiological functions in mammals. To increase our understanding of the origin and mechanisms of the complex NPY system, we report here the cloning and pharmacological characterization of receptors Y-1 and Y-5 in the first non-mammal, chicken (Gallus gallus). The receptors display 80-83% and 64-72% amino acid sequence identity, respectively, with their mammalian orthologues. The three endogenous ligands NPY, peptide YY (PYY) and pancreatic polypeptide (PP) have similar affinities as in mammals, i.e. NPY and PYY have subnanomolar affinity for both receptors whereas chicken PP bound with nanomolar affinity to Y-5 but not to Y-1. A notable difference to mammalian receptor subtypes is that the Y-1 antagonist SR120819A does not bind chicken Y-1, whereas BIBP3226 does, The Y-5 antagonist CGP71863A binds to the chicken Y-5 receptor. Anatomically, both Y-1 and Y-5 have high mRNA expression levels in the infundibular nucleus which is the homologous structure of the hypothalamic arcuate nucleus in mammals. These results suggest that some of the selective Y-1 and Y-5 antagonists developed in mammals can be used to study appetite regulation in chicken.