Isolation of new ligands for orphan receptor MRGPRX1-hemorphins LVV-H7 and VV-H7

- Two new ligands for the MRGPRX1 were isolated by consecutive HPLC purifications from human platelet preparation.
- The ligands were identified as LVV-hemorphin-7 and VV-hemorphin-7 with mass spectrometry.
- LVV-hemorphin-7 and VV-hemorphin-7 are dose dependently activating the MRGPRX1.

The human MAS-related G protein-coupled receptor X1 (MRGPRX1) is a member of the GPCR family. The receptor is primate specific and expressed in the sensory neurons of dorsal root ganglion and trigeminal ganglion, where it is considered to be involved in the pain perception. The MRGPRX1 has unusual binding mechanism, as it is activated by several different ligands as well as several different fragments of precursor proteins. Thus, we hypothesize that it is activated by several unknown compounds as well since the receptor is still classified as orphan. Here, we describe the isolation of two novel endogenous ligands for the MRGPRX1 from human platelet preparation. The isolated ligands are hemoglobin β-chain fragments, known members of the hemorphin family.