Pro-resolving G protein-coupled receptor

"Pro-resolving G protein-coupled receptors" is not a single molecular entity but rather refers collectively to a subset of GPCRs that bind specialized pro-resolving mediators (SPMs) such as resolvins, protectins, maresins, and lipoxins. These receptors, including FPR2/ALX, GPR32, GPR18, chemerin 1, BLT1, and GPR37, play essential roles in actively terminating inflammation and restoring tissue homeostasis. Upon activation by endogenous or synthetic agonists, pro-resolving GPCRs drive the resolution phase of inflammation by promoting neutrophil apoptosis, enhancing macrophage phagocytosis (efferocytosis), and suppressing pro-inflammatory signaling. The system demonstrates poly-pharmacology, as multiple SPMs activate several receptors and vice versa, and therapeutic targeting faces challenges of specificity, complex signaling, and limited clinical translation thus far. These GPCRs are increasingly recognized as attractive—but currently complex and partly experimental—therapeutic targets in diverse inflammatory, cardiovascular, metabolic, neurodegenerative diseases, and cancer[5][3][1][2][6][7].

Other names

SPM receptorSpecialized pro-resolving mediator receptorPro-resolving GPCRSPM GPCR

Receptor agonist—activation by SPMs promotes resolution of inflammation via signaling pathways that drive apoptosis and phagocytosis of neutrophils/macrophages - Biased agonism—preferential activation of pro-resolving signaling pathways over pro-inflammatory ones - Allosteric modulation—binding at alternative receptor sites for specificity and efficacy[5][7][8]