來自約翰霍普金斯大學醫(yī)學院感覺生物學，華盛頓大學醫(yī)學院的研究人員在上皮感覺神經細胞中發(fā)現了一個G蛋白偶聯受體家族成員：Mrgprs,，能形式瘙癢受體的功能,。這對于了解初級感覺神經細胞中組胺非依賴性瘙癢的分子和細胞機制具有重要的意義,。
領導這一研究的是約翰霍普金斯醫(yī)學院的董新中（Xinzhong Dong,，音譯）博士,，其入選了2009年早期職業(yè)科學家項目（2009 Early Career Scientist Program）,，是入選的4位華人科學家之一（這項計劃將在未來的6年中為每一位入選科學家提供包括薪酬,，福利和研究預算在內的,，超過150萬美元的經費支持），董博士主要從事疼痛相關神經細胞的分子與遺傳機制研究,。
瘙瘁是機體生理狀態(tài)下自我保護的一種反應機制,，也是許多系統(tǒng)性疾病和皮膚疾病的癥狀之一,。瘙癢有特異的神經傳導通路，表明瘙癢和疼痛是不同的獨立的感覺形式,。近年來的研究發(fā)現,，傳統(tǒng)的瘙瘁介質，如組胺,、血清素,、乙酰膽堿等，通過刺激C類神經纖維產生瘙癢,，此外,，在皮膚感覺神經纖維也發(fā)現有阿片樣肽、香草基衍生物等瘙癢介質的受體存在,，提示這些介質可能通過與皮膚感覺神經纖維的受體結合介導瘙瘁,。
瘙癢的產生是一個復雜的、多因素作用的結果,，其具體機制尚不完全清楚,，在這篇最新的文章中。研究人員在上皮感覺神經細胞中發(fā)現了一個G蛋白偶聯受體家族成員：Mrgprs,，能形式瘙癢受體的功能,。這對于了解初級感覺神經細胞中組胺非依賴性瘙癢的分子和細胞機制具有重要的意義。
研究人員進行了Mrgprs基因敲除實驗,，發(fā)現缺失了這一基因,，小鼠會出現CQ，而不是組胺誘導的瘙癢缺陷,，并且通過更進一步的研究證實Mrgprs這一基因也許就是瘙癢選擇性神經細胞行使功能的分子通道,，這為瘙癢治療提供了一個新的分子靶標。（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.
