来自约翰霍普金斯大学医学院感觉生物学，华盛顿大学医学院的研究人员在上皮感觉神经细胞中发现了一个G蛋白偶联受体家族成员：Mrgprs，能形式瘙痒受体的功能。这对于了解初级感觉神经细胞中组胺非依赖性瘙痒的分子和细胞机制具有重要的意义。
领导这一研究的是约翰霍普金斯医学院的董新中（Xinzhong Dong，音译）博士，其入选了2009年早期职业科学家项目（2009 Early Career Scientist Program），是入选的4位华人科学家之一（这项计划将在未来的6年中为每一位入选科学家提供包括薪酬，福利和研究预算在内的，超过150万美元的经费支持），董博士主要从事疼痛相关神经细胞的分子与遗传机制研究。
瘙瘁是机体生理状态下自我保护的一种反应机制，也是许多系统性疾病和皮肤疾病的症状之一。瘙痒有特异的神经传导通路，表明瘙痒和疼痛是不同的独立的感觉形式。近年来的研究发现，传统的瘙瘁介质，如组胺、血清素、乙酰胆碱等，通过刺激C类神经纤维产生瘙痒，此外，在皮肤感觉神经纤维也发现有阿片样肽、香草基衍生物等瘙痒介质的受体存在，提示这些介质可能通过与皮肤感觉神经纤维的受体结合介导瘙瘁。
瘙痒的产生是一个复杂的、多因素作用的结果，其具体机制尚不完全清楚，在这篇最新的文章中。研究人员在上皮感觉神经细胞中发现了一个G蛋白偶联受体家族成员：Mrgprs，能形式瘙痒受体的功能。这对于了解初级感觉神经细胞中组胺非依赖性瘙痒的分子和细胞机制具有重要的意义。
研究人员进行了Mrgprs基因敲除实验，发现缺失了这一基因，小鼠会出现CQ，而不是组胺诱导的瘙痒缺陷，并且通过更进一步的研究证实Mrgprs这一基因也许就是瘙痒选择性神经细胞行使功能的分子通道，这为瘙痒治疗提供了一个新的分子靶标。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
