MRGPRX1

G protein-coupled receptor specifically expressed in sensory neurons of dorsal root ganglion, and which is involved in itch perception and pain transmission. Specifically activated by a variety of enkephalin (PENK) neuropeptides, such as BAM22 and BAM8-22, which induce itch in a histamine-independent manner. Activated by some tick defensins, such as I.persulcatus Def1 and I.ricinus Def2, evoking itch. Also activated by conotoxin CNF-Tx2, inducing itch sensation. Activated by the antimalarial drug chloroquine; however, activation requires concentrations that exceed the chloroquine concentrations observed in plasma of patients undergoing chloroquine treatment. Also activated following cleavage by the dust mite cysteine protease Der p1. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. MRGPRX1 is both coupled to G(q) and G(i) G proteins: G(q) coupling activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers, leading to sensitize TRPV1 in pruriceptors, while G(i) coupling mediates inhibition of adenylate cyclase activity. Activation of MRGPRX1 in the peripheral nervous system elicits itch, evoking scratching. MRGPRX1 activation in sensory neurons of the nasal mucosa mediates sneezing responses to irritants or influenza-virus (By similarity). Activation in the central nervous system dampens chronic pain: BAM8-22-binding at the central terminals prevents pain signals passing to spinal cord neurons, attenuating spinal nociceptive transmission. Activation by CXCL17 induces chemotactic movement..

Function from UniProtKB (Q96LB2), read 2026-09-23. CC BY 4.0.