Mas-related G protein-coupled receptor member D (MRGPRD)

Mas-related G protein-coupled receptor member D (MRGPRD) is a member of the MAS-related GPCR family highly expressed in sensory neurons (particularly dorsal root ganglion), cardiovascular tissue, mast cells, macrophages, and certain tumors. This receptor mediates pain and itch signals, inflammatory cytokine release (notably IL-6), and is activated by β-alanine, alamandine, angiotensin II, and 5-oxoeicosatetraenoic acid. Structurally, MrgD features a shallow ligand-binding pocket and unique disulfide bonding characteristics, distinguishing its activation mode from classic class A GPCRs. Pathophysiologically, MRGPRD is implicated in neuropathic pain, cold allodynia, cardiovascular function, pseudorelergic reactions, certain cancers, and osteocyte survival. Its high basal activity and ligand promiscuity pose challenges for drug development and in vitro screening, but also point to its role in constitutive cellular signaling and modulation.

Other names

MrgDMRGDmrgDBeta-alanine receptorG-protein coupled receptor TGR7TGR7MAS-related GPR member Dmas-related G protein-coupled MRGDMAS-related G protein-coupled receptor member D

Agonists like β-alanine activate the MRGPRD, triggering Gq-mediated phospholipase C (PLC) pathway, leading to IP3/DAG formation and release of inflammatory mediators (e.g., IL-6). Also couples to Gi, modulating cAMP and KCNQ channels, increasing neuronal excitability (pain/itch). Activation leads to inactivation of KCNQ channels, increased neuronal excitation, and sensation of pain and itch. Alamandine/Ang(1-7) activation leads to NO release, counteracting cardiovascular fibrosis/hypertension.