MOLECULAR CHARACTERIZATION OF A 2ND MELATONIN RECEPTOR EXPRESSED IN HUMAN RETINA AND BRAIN - THE MEL(1B) MELATONIN RECEPTOR
MOLECULAR CHARACTERIZATION OF A 2ND MELATONIN RECEPTOR EXPRESSED IN HUMAN RETINA AND BRAIN - THE MEL(1B) MELATONIN RECEPTOR
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DOI：
10.1073/pnas.92.19.8734
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发表时间：
1995-09-12
影响因子：
11.1
通讯作者：
GUSELLA, JF
中科院分区：
文献类型：
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作者：
REPPERT, SM;GODSON, C;GUSELLA, JF
松果体激素褪黑素的G蛋白偶联受体是最近从哺乳动物中克隆的，命名为Mel(1a)褪黑激素受体。我们现在报道从人类中克隆第二个G蛋白偶联的褪黑素受体，并将其命名为MEL(1b)褪黑素受体。MEL(1b)受体基因编码一个362个氨基酸的蛋白质，在氨基酸水平上与人的MEL(1a)受体有60%的同源性。MEL(1b)受体在COS-1细胞中的瞬时表达导致高亲和力的2-[I-125]碘黑素结合(K-d=160+/-30 pm)。此外，8种配体对特异性2-[125I]碘黑素结合的抑制顺序与Mel(1a)褪黑素受体相似。对稳定表达Mel(1b)褪黑素受体的NIH3T3细胞的功能研究表明，它与腺苷环化酶的抑制有关。比较逆转录聚合酶链式反应显示Mel(1b)褪黑素受体在视网膜和脑中表达，人-啮齿类体细胞杂交的PCR分析将Mel(1b)受体基因(MTNR1B)定位于人类染色体11q21-22。Mel(1b)褪黑素受体可能介导了已报道的褪黑素在视网膜中的作用，并参与了褪黑素在哺乳动物中的一些神经生物学效应。
A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated the Mel(1a) melatonin receptor. We now report the cloning of a second G protein-coupled melatonin receptor from humans and designate it the Mel(1b) melatonin receptor. The Mel(1b) receptor cDNA encodes a protein of 362 amino acids that is 60% identical at the amino acid level to the human Mel(1a) receptor. Transient expression of the Mel(1b) receptor in COS-1 cells results in high-affinity 2-[I-125]iodomelatonin binding (K-d = 160 +/- 30 pM) In addition, the rank order of inhibition of specific 2-[125I]iodomelatonin binding by eight ligands is similar to that exhibited by the Mel(1a) melatonin receptor. Functional studies of NIH 3T3 cells stably expressing the Mel(1b) melatonin receptor indicate that it is coupled to inhibition of adenylyl cyclase. Comparative reverse transcription PCR shows that the Mel(1b) melatonin receptor is expressed in retina and, to a lesser extent, brain, PCR analysis of human-rodent somatic cell hybrids maps the Mel(1b) receptor gene (MTNR1B) to human chromosome 11q21-22. The Mel(1b) melatonin receptor may mediate the reported actions of melatonin in retina and participate in some of the neurobiological effects of melatonin in mammals.