Mas-related G protein-coupled receptor family (MRGPR (when referring to the family), specific receptors have abbreviations such as MRGPRX1, MRGPRD, MRGPRX2, etc.)

The "itch receptor" refers to a set of molecular receptors, predominantly members of the Mas-related G protein-coupled receptor (MRGPR) family, which are essential for detecting and transmitting itch (pruritus) signals in the peripheral and central nervous systems. These GPCRs are mainly localized to subsets of sensory neurons in the dorsal root ganglia and play distinct roles in different types of itch (histaminergic, non-histaminergic, cholestatic, etc.), as well as in mast cells (notably, MRGPRX2). They are activated by both exogenous (e.g., drugs like chloroquine, β-alanine) and endogenous ligands (e.g., peptides such as BAM8-22, bile acids), resulting in the transmission of the itch sensation to the central nervous system. Other related receptors involved in itch include histamine receptors, protease-activated receptors (PAR2), and the gastrin-releasing peptide receptor (GRPR), but the most direct link to "itch receptor" nomenclature is with the MRGPR family. Dysregulation or aberrant activation of these pathways is implicated in chronic pruritic diseases and forms a focus for the development of antipruritic therapeutics[1][2][5][8].

Other names

Itch-sensing receptorPruriceptorPruritic GPCRItch GPCRMas-related G protein-coupled receptorMRGPR familyItch-specific receptorPruriceptive receptor

Agonists binding to GPCRs on sensory neurons, causing neuronal firing and transmission of the itch signal[1][2][8] Activation of mast cells (MRGPRX2), leading to histamine-independent itch[1] Downstream activation of calcium channels and G-protein signaling