Cloning and characterization of a novel receptor to pancreatic polypeptide, a member of the neuropeptide Y receptor family
Cloning and characterization of a novel receptor to pancreatic polypeptide, a member of the neuropeptide Y receptor family
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DOI：
10.1016/0014-5793(96)00067-1
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发表时间：
1996-02-26
期刊：
影响因子：
3.5
通讯作者：
Cornfield, LJ
中科院分区：
文献类型：
--
作者：
Gregor, P;Millham, ML;Cornfield, LJ
我们报道了小鼠基因NPYR-D的分离，该基因预测了375个氨基酸的无内含子的新型G蛋白偶联受体，NPYR-D与克隆的Y1， Y2，大鼠Y4/PP1和人类Y4/PP1受体的同源性分别为45%，32%，92%和76%，Southern blots表明NPYR-D和人类Y4/PP1受体基因是物种同源的。大鼠[I-125]胰腺多肽（[I-125]rPP）以高亲和力结合npyr - d转染的COS-7细胞膜，即IC50=90 pM。[I-125]rPP结合的药理学特征显示，PP b> > PYY的效价顺序大于或等于NPY，因此PYY和NPY比PP弱至少5000倍。有趣的是，[I-125]rPYY结合的效价顺序相同，但PYY和NPY仅比Pa弱25倍，其IC50值约为120 pM。小鼠和人类的组织分布研究表明，这种新型受体在胃肠道、心脏、前列腺以及神经和内分泌信号传导中具有潜在的作用。
We report isolation of a murine gene, NPYR-D, which predicts an intronless novel G protein-coupled receptor of 375 amino acids, Percent identities of NPYR-D to the cloned Y1, Y2, rat Y4/PP1 and human Y4/PP1 receptors are 45, 32, 92 and 76, respectively, Southern blots indicate that NPYR-D and human Y4/PP1 receptor genes are species homologues. Rat [I-125]pancreatic polypeptide ([I-125]rPP) bound to NPYR-D-transfected COS-7 cell membranes with a high affinity, i.e. IC50=90 pM. Pharmacological characterization of [I-125]rPP binding showed a rank order of potency of PP >> PYY greater than or equal to NPY, such that PYY and NPY were at least 5000-fold weaker than PP. Interestingly, [I-125]rPYY binding produced the same rank order, but PYY and NPY were only 25-fold weaker than Pa, which had an IC50 value of approximately 120 pM. Tissue distribution studies in mouse and humans suggest potential roles of this novel receptor in the gastrointestinal tract, heart, prostate, as well as in neural and endocrine signalling.