Dr. Yulong Li published a paper in eLife with his collaborators.
Patients with liver diseases often suffer chronic itching, yet the pruritogen(s) and receptor(s) remain largely elusive. Here, they 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, both bile acids and a MRGPRX4 specific agonist induced itching in human subjects. However, a specific agonist for another bile acid receptor, TGR5, failed to induce itching in human subjects and they found that TGR5 is not expressed in human hDRG neurons. Finally, they showed a positive correlation between cholestatic itching and plasma bile acids level in itchy patients, and that the elevated bile acids are sufficient to activate MRGPRX4. Taken together, these results strongly suggest that MRGPRX4 is a novel bile acid receptor that underlies cholestatic itching in human, providing a promising new drug target for anti-itch therapies.
Original link: https://doi.org/10.7554/eLife.48431
