Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced Pruritus

Qin Liu, Zongxiang Tang, Lenka Surdenikova, Seungil Kim, Kush N. Patel, Andrew Kim, Fei Ru, Yun Guan, Hao Jui Weng, Yixun Geng, Bradley J. Undem, Marian Kollarik, Zhou Feng Chen, David J. Anderson, Xinzhong Dong

研究成果: 雜誌貢獻文章同行評審

521 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)1353-1365
頁數13
期刊Cell
139
發行號7
DOIs
出版狀態已發佈 - 12月 24 2009

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)

指紋

深入研究「Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced Pruritus」主題。共同形成了獨特的指紋。

引用此