來(lái)自約翰霍普金斯大學(xué)醫(yī)學(xué)院感覺(jué)生物學(xué),，華盛頓大學(xué)醫(yī)學(xué)院的研究人員在上皮感覺(jué)神經(jīng)細(xì)胞中發(fā)現(xiàn)了一個(gè)G蛋白偶聯(lián)受體家族成員：Mrgprs,，能形式瘙癢受體的功能,。這對(duì)于了解初級(jí)感覺(jué)神經(jīng)細(xì)胞中組胺非依賴(lài)性瘙癢的分子和細(xì)胞機(jī)制具有重要的意義,。
領(lǐng)導(dǎo)這一研究的是約翰霍普金斯醫(yī)學(xué)院的董新中（Xinzhong Dong,，音譯）博士,，其入選了2009年早期職業(yè)科學(xué)家項(xiàng)目（2009 Early Career Scientist Program）,，是入選的4位華人科學(xué)家之一（這項(xiàng)計(jì)劃將在未來(lái)的6年中為每一位入選科學(xué)家提供包括薪酬，福利和研究預(yù)算在內(nèi)的,，超過(guò)150萬(wàn)美元的經(jīng)費(fèi)支持）,，董博士主要從事疼痛相關(guān)神經(jīng)細(xì)胞的分子與遺傳機(jī)制研究。
瘙瘁是機(jī)體生理狀態(tài)下自我保護(hù)的一種反應(yīng)機(jī)制,，也是許多系統(tǒng)性疾病和皮膚疾病的癥狀之一,。瘙癢有特異的神經(jīng)傳導(dǎo)通路，表明瘙癢和疼痛是不同的獨(dú)立的感覺(jué)形式,。近年來(lái)的研究發(fā)現(xiàn),，傳統(tǒng)的瘙瘁介質(zhì),，如組胺,、血清素、乙酰膽堿等,，通過(guò)刺激C類(lèi)神經(jīng)纖維產(chǎn)生瘙癢,，此外，在皮膚感覺(jué)神經(jīng)纖維也發(fā)現(xiàn)有阿片樣肽,、香草基衍生物等瘙癢介質(zhì)的受體存在,，提示這些介質(zhì)可能通過(guò)與皮膚感覺(jué)神經(jīng)纖維的受體結(jié)合介導(dǎo)瘙瘁。
瘙癢的產(chǎn)生是一個(gè)復(fù)雜的,、多因素作用的結(jié)果,，其具體機(jī)制尚不完全清楚，在這篇最新的文章中,。研究人員在上皮感覺(jué)神經(jīng)細(xì)胞中發(fā)現(xiàn)了一個(gè)G蛋白偶聯(lián)受體家族成員：Mrgprs,，能形式瘙癢受體的功能。這對(duì)于了解初級(jí)感覺(jué)神經(jīng)細(xì)胞中組胺非依賴(lài)性瘙癢的分子和細(xì)胞機(jī)制具有重要的意義,。
研究人員進(jìn)行了Mrgprs基因敲除實(shí)驗(yàn),，發(fā)現(xiàn)缺失了這一基因，小鼠會(huì)出現(xiàn)CQ,，而不是組胺誘導(dǎo)的瘙癢缺陷,，并且通過(guò)更進(jìn)一步的研究證實(shí)Mrgprs這一基因也許就是瘙癢選擇性神經(jīng)細(xì)胞行使功能的分子通道，這為瘙癢治療提供了一個(gè)新的分子靶標(biāo),。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, 10 December 2009 doi:10.1016/j.cell.2009.11.034
Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced Pruritus
Qin Liu1, Zongxiang Tang1, Lenka Surdenikova2, 4, Seungil Kim5, Kush N. Patel1, Andrew Kim1, Fei Ru2, Yun Guan3, Hao-Jui Weng1, Yixun Geng1, Bradley J. Undem2, Marian Kollarik2, Zhou-Feng Chen5, David J. Anderson6, 7 and Xinzhong Dong1, 7, ,
1 The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
2 Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
3 Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
4 Department of Pathophysiology, Jessenius Medical School, 037 53 Martin, Slovakia
5 Departments of Anesthesiology, Psychiatry, and Developmental Biology, Washington University School of Medicine Pain Center, St. Louis, MO 63110, USA
6 Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
7 Howard Hughes Medical Institute
The cellular and molecular mechanisms mediating histamine-independent itch in primary sensory neurons are largely unknown. Itch induced by chloroquine (CQ) is a common side effect of this widely used antimalarial drug. Here, we show that Mrgprs, a family of G protein-coupled receptors expressed exclusively in peripheral sensory neurons, function as itch receptors. Mice lacking a cluster of Mrgpr genes display significant deficits in itch induced by CQ but not histamine. CQ directly excites sensory neurons in an Mrgpr-dependent manner. CQ specifically activates mouse MrgprA3 and human MrgprX1. Loss- and gain-of-function studies demonstrate that MrgprA3 is required for CQ responsiveness in mice. Furthermore, MrgprA3-expressing neurons respond to histamine and coexpress gastrin-releasing peptide, a peptide involved in itch sensation, and MrgprC11. Activation of these neurons with the MrgprC11-specific agonist BAM8-22 induces itch in wild-type but not mutant mice. Therefore, Mrgprs may provide molecular access to itch-selective neurons and constitute novel targets for itch therapeutics.
