Daphne Chun-Che Chien, Nathachit Limjunyawong, Can Cao, James Meixiong, Qi Peng, Cheng-Ying Ho, Jonathan F Fay, Bryan L Roth, Xinzhong Dong
The phosphate modification of drugs is a common chemical strategy to increase solubility and allow for parenteral administration. Unfortunately, phosphate modifications often elicit treatment- or dose-limiting pruritus through an unknown mechanism. Using unbiased high-throughput drug screens, we identified the Mas-related G protein-coupled receptor X4 (MRGPRX4), a primate-specific, sensory neuron receptor previously implicated in itch, as a potential target for phosphate-modified compounds. Using both Gq -mediated calcium mobilization and G protein-independent GPCR assays, we found that phosphate-modified compounds potently activate MRGPRX4...
May 8, 2024: Science Translational Medicine