Jennings C A, Harrison D C, Maycox P R, Crook B, Smart D, Hervieu G J
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
Neuroscience. 2003;120(2):309-24. doi: 10.1016/s0306-4522(03)00260-4.
Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor that shares between 47 and 51% homology with other known bombesin receptors. The natural ligand for BRS-3 is currently unknown and little is known about the mechanisms regulating BRS-3 gene expression. Unlike other mammalian bombesin receptors that have been shown to be predominantly expressed in the CNS and gastrointestinal tract, expression of the BRS-3 receptor in the rat brain has previously not been observed. To gain further understanding of the biology of BRS-3, we have studied the distribution of BRS-3 mRNA and protein in the rat CNS. The mRNA expression pattern was studied using reverse transcription followed by quantitative polymerase chain reaction. Using immunohistological techniques, the distribution of BRS-3 protein in the rat brain was investigated using a rabbit affinity-purified polyclonal antiserum raised against an N-terminal peptide. The BRS-3 receptor was found to be widely expressed in the rat brain at both mRNA and protein levels. Particularly strong immunosignals were observed in the cerebral cortex, hippocampal formation, hypothalamus and thalamus. Other regions of the brain such as the basal ganglia, midbrain and reticular formation were also immunopositive for BRS-3. In conclusion, our neuroanatomical data provide evidence that BRS-3 is as widely expressed in the rat brain as other bombesin-like peptide receptors and suggest that this receptor may also have important roles in the CNS, mediating the functions of a so far unidentified ligand.
胃泌素释放肽受体亚型3(BRS - 3)是一种孤儿G蛋白偶联受体,与其他已知的胃泌素释放肽受体具有47%至51%的同源性。目前尚不清楚BRS - 3的天然配体,对调节BRS - 3基因表达的机制也知之甚少。与其他已证明主要在中枢神经系统和胃肠道表达的哺乳动物胃泌素释放肽受体不同,此前未在大鼠脑中观察到BRS - 3受体的表达。为了进一步了解BRS - 3的生物学特性,我们研究了BRS - 3 mRNA和蛋白在大鼠中枢神经系统中的分布。使用逆转录随后进行定量聚合酶链反应研究mRNA表达模式。利用免疫组织学技术,使用针对N端肽产生的兔亲和纯化多克隆抗血清研究BRS - 3蛋白在大鼠脑中的分布。发现BRS - 3受体在大鼠脑的mRNA和蛋白水平均广泛表达。在大脑皮层、海马结构、下丘脑和丘脑观察到特别强的免疫信号。大脑的其他区域,如基底神经节、中脑和网状结构,对BRS - 3也呈免疫阳性。总之,我们的神经解剖学数据提供了证据,表明BRS - 3在大鼠脑中的表达与其他胃泌素释放肽样肽受体一样广泛,并表明该受体可能在中枢神经系统中也具有重要作用,介导一种迄今未鉴定配体的功能。