Mas-related G protein-coupled receptor (Mrgpr)

Mas-related G protein-coupled receptors (Mrgprs) are a large subfamily of G protein-coupled receptors, first identified for their role in sensory neurons and later characterized as key regulators in pruriception (itch), nociception (pain), mast cell activation, and innate immunity[1][5][7]. They are predominantly expressed in small-diameter primary sensory neurons (e.g., dorsal root ganglia) and mast cells, where they mediate responses to a wide variety of endogenous and exogenous ligands, including neuropeptides, antimicrobial peptides, and small molecule drugs[1][4][7]. The MRGPRX2 subtype in humans is a prominent mediator of IgE-independent mast cell activation, contributing to allergic and inflammatory diseases, pseudoallergic drug reactions, and neurogenic inflammation[6][7][8]. Experimental small molecule antagonists such as PSB-172656 have shown efficacy in selectively blocking MRGPRX2 activation and downstream hypersensitivity reactions in preclinical models[4]. The family remains of strong interest as a therapeutic target for chronic pain, chronic pruritus, allergic/inflammatory conditions, and as a mechanism for adverse drug reactions[3][6][7]. Their full physiological roles and therapeutic potential continue to be actively explored.

Other names

MrgprsMAS-related G protein-coupled receptorsMas-related G protein-coupled receptor-X2 (MRGPRX2) (for the human mast cell-specific subtype)MAS1-related G protein-coupled receptor familyMas gene-related G protein-coupled receptors

Antagonism of MRGPRX2-mediated activation (for antagonists, e.g., PSB-172656) Inhibition of mast cell degranulation (for antagonists) Activation of mast cell degranulation (for agonists, e.g., certain peptides or drugs) Modulation of nociceptive and pruriceptive signaling