G protein-coupled receptor for specialized pro-resolving mediator

G protein-coupled receptors for specialized pro-resolving mediators (SPM GPCRs) are a set of receptors belonging to the GPCR superfamily that recognize and are activated by endogenous lipid mediators—resolvins, lipoxins, protectins, and maresins—which drive the active resolution of inflammation and restore tissue homeostasis. Major examples include formyl peptide receptor 2 (FPR2/ALX), chemerin receptor 1 (ChemR23), G protein-coupled receptor 18 (GPR18), G protein-coupled receptor 32 (GPR32), G protein-coupled receptor 37 (GPR37), and leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6). These receptors are implicated in immune cell trafficking, clearance of apoptotic cells, suppression of pro-inflammatory signals, and modulation of pain and tissue regeneration. Pharmacological targeting of these SPM GPCRs represents a novel therapeutic strategy for treating chronic inflammation, pain, and autoimmunity, but drug development remains at an early stage and not all receptor–ligand pairings have consistent experimental validation.

Other names

SPM receptorSpecialized pro-resolving mediator receptorSPM GPCRSPM-binding G protein-coupled receptor

Agonist at SPM receptor (GPCR) Positive allosteric modulator (for example, of prostaglandin E2 receptor EP4) Induction of anti-inflammatory and pro-resolving signaling pathways, including enhanced cAMP formation, Gi signaling initiation, inhibition of neutrophil recruitment, and promotion of efferocytosis and tissue repair