Mas-related G protein-coupled receptor (MRGPR) (MRGPR)

The Mas-related G protein-coupled receptor (MRGPR) family consists of Class A GPCRs that are predominantly expressed in small-diameter sensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia, as well as on mast cells [3, 11, 14]. Originally characterized as sensory neuron-specific receptors (SNSRs), these receptors play a pivotal role in somatosensation, particularly in mediating non-histaminergic itch and modulating pain signaling [3, 4, 11]. In humans, the family includes key members such as MRGPRX1, MRGPRX2, MRGPRX4, and MRGPRD, which serve as distinct therapeutic targets for various conditions [3, 14]. MRGPRX1 is primarily targeted for the treatment of chronic and neuropathic pain through agonism, which inhibits nociceptive transmission in the spinal cord [5, 12]. Conversely, MRGPRX2 is a major mediator of IgE-independent mast cell degranulation, making its antagonism a strategy for treating atopic dermatitis, chronic urticaria, and drug-induced pseudo-allergic reactions [10, 16]. MRGPRX4 has emerged as a receptor for bile acids and bilirubin, contributing to cholestatic and uremic pruritus [3, 14]. Despite their therapeutic promise, drug development is complicated by significant species-specific differences between rodents and humans, as well as high genetic polymorphism within the human population [3, 9, 10].

Other names

Mas-related gene receptorSensory neuron-specific receptorSNSRMRG

Agonism of MRGPRX1 for analgesia; Antagonism of MRGPRX2 for anti-inflammatory and anti-itch effects; Antagonism of MRGPRX4 for pruritus relief