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MRGPRX4 is a bile acid receptor for human cholestatic itch.

Huasheng Yu | Tianjun Zhao | Simin Liu | Qinxue Wu | Omar Johnson | Zhaofa Wu | Zihao Zhuang | Yaocheng Shi | Luxin Peng | Renxi He | Yong Yang | Jianjun Sun | Xiaoqun Wang | Haifeng Xu | Zheng Zeng | Peng Zou | Xiaoguang Lei | Wenqin Luo | Yulong Li
eLife | 2019

Patients with liver diseases often suffer from chronic itch, yet the pruritogen(s) and receptor(s) remain largely elusive. Here, we identify bile acids as natural ligands for MRGPRX4. MRGPRX4 is expressed in human dorsal root ganglion (hDRG) neurons and co-expresses with itch receptor HRH1. Bile acids elicited Ca2+ responses in cultured hDRG neurons, and bile acids or a MRGPRX4 specific agonist induced itch in human subjects. However, a specific agonist for another bile acid receptor TGR5 failed to induce itch in human subjects and we find that human TGR5 is not expressed in hDRG neurons. Finally, we show positive correlation between cholestatic itch and plasma bile acids level in itchy patients and the elevated bile acids is sufficient to activate MRGPRX4. Taken together, our data strongly suggest that MRGPRX4 is a novel bile acid receptor that likely underlies cholestatic itch in human, providing a promising new drug target for anti-itch therapies.

Pubmed ID: 31500698

Associated grants

  • Agency: Department of the Central Committee of the CPC, International
    Id: Junior Thousand Talents Program of China
  • Agency: Chinese Institute for Brain Research, International
    Id: Z181100001518004
  • Agency: University of Pennsylvania, International
    Id: Internal funding

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