Mrgprx1, a Mas-related G protein-coupled receptor (MRGPR), is a key player in itch perception. It is preferentially expressed in small-diameter primary sensory neurons and is involved in the mediation of nociception and pruritus [4,5,6]. Activation of Mrgprx1 can trigger itch-related responses, making it a potential target for treating chronic itch and pain [1].

Studies have shown that activation of Mrgprx1 by BAM8-22 can trigger action potential discharges in dorsal root ganglion (DRG) neurons. This is achieved by lowering the activation threshold of TTX-resistant sodium channels and inducing inward sodium currents, and Nav1.9 knockout significantly reduces BAM8-22 evoked scratching behavior, suggesting that Mrgprx1-induced itch sensation is related to the activity of TTX-resistant voltage-gated sodium channels [3]. In addition, Mrgprx1 activation can degranulate mast cells, contributing to the development of neurogenic inflammation [2]. Berbamine, an inhibitor of Mrgprx1, can significantly reduce chloroquine-induced itch in mice, indicating its potential as a drug candidate for treating chloroquine-induced pruritus [7].

In conclusion, Mrgprx1 plays a crucial role in itch sensation and related inflammatory processes. Research using gene-knockout models, like the Nav1.9 knockout in relation to Mrgprx1-mediated itch, has provided insights into the mechanisms underlying these biological functions. Understanding Mrgprx1 can potentially lead to new therapeutic strategies for treating itch-related and pain-related diseases.

References:

1. Guo, Lulu, Zhang, Yumu, Fang, Guoxing, Eric Xu, H, Sun, Jin-Peng. 2023. Ligand recognition and G protein coupling of the human itch receptor MRGPRX1. In Nature communications, 14, 5004. doi:10.1038/s41467-023-40705-z. https://pubmed.ncbi.nlm.nih.gov/37591889/

2. Choi, Jae Eun, Di Nardo, Anna. 2018. Skin neurogenic inflammation. In Seminars in immunopathology, 40, 249-259. doi:10.1007/s00281-018-0675-z. https://pubmed.ncbi.nlm.nih.gov/29713744/

3. Tseng, Pang-Yen, Zheng, Qin, Li, Zhe, Dong, Xinzhong. 2019. MrgprX1 Mediates Neuronal Excitability and Itch Through Tetrodotoxin-Resistant Sodium Channels. In Itch (Philadelphia, Pa.), 4, . doi:10.1097/itx.0000000000000028. https://pubmed.ncbi.nlm.nih.gov/33442562/

4. Liu, Yongfeng, Cao, Can, Huang, Xi-Ping, Fay, Jonathan F, Roth, Bryan L. 2022. Ligand recognition and allosteric modulation of the human MRGPRX1 receptor. In Nature chemical biology, 19, 416-422. doi:10.1038/s41589-022-01173-6. https://pubmed.ncbi.nlm.nih.gov/36302898/

5. Al Hamwi, Ghazl, Riedel, Yvonne K, Clemens, Sophie, Thimm, Dominik, Müller, Christa E. 2022. MAS-related G protein-coupled receptors X (MRGPRX): Orphan GPCRs with potential as targets for future drugs. In Pharmacology & therapeutics, 238, 108259. doi:10.1016/j.pharmthera.2022.108259. https://pubmed.ncbi.nlm.nih.gov/35934214/

6. Gan, Bing, Yu, Leiye, Yang, Haifeng, Cao, Zhijian, Ren, Ruobing. 2023. Mechanism of agonist-induced activation of the human itch receptor MRGPRX1. In PLoS biology, 21, e3001975. doi:10.1371/journal.pbio.3001975. https://pubmed.ncbi.nlm.nih.gov/37347749/

7. Ryu, Kunhi, Heo, Yunkyung, Lee, Yechan, Jeon, Hyejin, Namkung, Wan. 2022. Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1. In International journal of molecular sciences, 23, . doi:10.3390/ijms232214321. https://pubmed.ncbi.nlm.nih.gov/36430803/