神经肽Y受体的多样性：斑马鱼中第三种不同亚型的克隆

Multiplicity of neuropeptide Y receptors: cloning of a third distinct subtype in the zebrafish.

作者信息

Ringvall M, Berglund M M, Larhammar D

机构信息

Department of Medical Pharmacology, Uppsala University, Sweden.

出版信息

Biochem Biophys Res Commun. 1997 Dec 29;241(3):749-55. doi: 10.1006/bbrc.1997.7886.

DOI:10.1006/bbrc.1997.7886

PMID:9434780

Abstract

Five different receptor subtypes for neuropeptide Y (NPY) have recently been cloned in mammals. We have discovered three distinct subtypes by PCR in the zebrafish, Danio rerio, and describe here one of these called zYc. The protein sequence identity is 46-51% to mammalian subtypes Y1, Y4 and Y6 and to zebrafish Ya, i.e., the same degree of identity as these subtypes display to one another. The identity to zYb is higher, 75%, indicating that zYb and zYc share a more recent ancestor. The zYc receptor binds NPY and PYY (peptide YY) from mammals as well as zebrafish with high affinities and has a Kd of 16 pM for 125I-pPYY. The pharmacological profile is similar to, but distinct-from, mammalian Y1. zYc inhibits cAMP synthesis. This work suggests that NPY has more receptor subtypes than any other peptide that binds to G protein-coupled receptors. Work is in progress to see if the zebrafish receptors are present in mammals.

摘要

最近在哺乳动物中克隆出了神经肽Y（NPY）的五种不同受体亚型。我们通过聚合酶链反应（PCR）在斑马鱼（Danio rerio）中发现了三种不同的亚型，并在此描述其中一种名为zYc的亚型。其蛋白质序列与哺乳动物的Y1、Y4和Y6亚型以及斑马鱼的Ya亚型的一致性为46%-51%，即这些亚型之间的一致性程度相同。与zYb的一致性更高，为75%，这表明zYb和zYc有更近的共同祖先。zYc受体以高亲和力结合来自哺乳动物以及斑马鱼的NPY和肽YY（PYY），对125I-pPYY的解离常数（Kd）为16皮摩尔。其药理学特征与哺乳动物的Y1相似，但又有所不同。zYc抑制环磷酸腺苷（cAMP）的合成。这项研究表明，NPY的受体亚型比任何其他与G蛋白偶联受体结合的肽都要多。目前正在进行研究，以确定斑马鱼的这些受体在哺乳动物中是否存在。