ORL1, A NOVEL MEMBER OF THE OPIOID RECEPTOR FAMILY - CLONING, FUNCTIONAL EXPRESSION AND LOCALIZATION
ORL1, A NOVEL MEMBER OF THE OPIOID RECEPTOR FAMILY - CLONING, FUNCTIONAL EXPRESSION AND LOCALIZATION
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DOI：
10.1016/0014-5793(94)80235-1
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发表时间：
1994-03-14
期刊：
影响因子：
3.5
通讯作者：
MEUNIER, JC
中科院分区：
文献类型：
--
作者：
MOLLEREAU, C;PARMENTIER, M;MEUNIER, JC
用编码阿片受体和生长抑素受体高度保守区域的寡核苷酸选择性地聚合酶链式反应扩增人和小鼠基因组DNA，产生了人DNA探针(hOP01,761bp)和小鼠DNA探针(mOP86,447bp)。用hOP01从人脑干中筛选出一个cDNA文库。一个克隆(命名为hORL1)被分离和测序，编码一个370个氨基酸的蛋白质，其一级结构显示了G蛋白偶联的膜受体的七个跨膜结构域。HORL1受体与阿片受体的关系最密切，不仅在结构上(序列)，而且在功能上：hORL1与小鼠的u-阿片受体、β-阿片受体和kappa-阿片受体有49%-50%的同源性，在稳定转染PRC/CMV：hORL1结构的CHO-K1细胞中，ORL1介导‘通用’(非选择性)阿片激动剂依托啡对腺苷酸环化酶的抑制。然而，hORL1似乎不是一个典型的阿片受体。它既不是生长抑素，也不是Delta型(N-烯丙基去甲氧唑碱)受体。与mOP86互补的合成寡核苷酸杂交的mRNAs存在于小鼠大脑和脊髓的许多区域，特别是边缘(杏仁核、海马体、隔区、缰核等)。和下丘脑结构。我们的结论是，hORL1受体是阿片受体家族的一个新成员，在调节包括本能行为和情绪在内的许多大脑功能方面具有潜在的作用。
Selective PCR amplification of human and mouse genomic DNAs with oligonucleotides encoding highly conserved regions of the delta-opioid and somatostatin receptors generated a human DNA probe (hOP01, 761 bp) and its murine counterpart (mOP86, 447 bp). hOP01 was used to screen a cDNA library from human brainstem. A clone (named hORL1) was isolated, sequenced and found to encode a protein of 370 amino acids whose primary structure displays the seven putative membrane-spanning domains of a G protein-coupled membrane receptor. The hORL1 receptor is most closely related to opioid receptors not only on structural (sequence) but also on functional grounds: hORL1 is 49-50% identical to the murine mu-, delta- and kappa-opioid receptors and, in CHO-K1 cells stably transfected with a pRc/CMV:hORL1 construct, ORL1 mediates inhibition of adenylyl cyclase by etorphine, a 'universal' (nonselective) opiate agonist. Yet, hORL1 appears not to be a typical opioid receptor. Neither is it a somatostatin or delta (N-allylnormetazocine) receptor. mRNAs hybridizing with synthetic oligonucleotides complementary to mOP86 are present in many regions of the mouse brain and spinal cord, particularly in limbic (amygdala, hippocampus, septum, habenula,...) and hypothalamic structures. We conclude that the hORL1 receptor is a new member of the opioid receptor family with a potential role in modulating a number of brain functions, including instinctive behaviours and emotions.