P2Y11 Receptor

P2Y11 receptor is a human purinergic receptor coupled to phosphoinositide and cyclic AMP signaling^[1]. ATP, ATPγS, BzATP, dATP, and AR-C67085 activate recombinant human P2Y11 receptor, while ADPβS, AMPαS, and A3P5PS act as partial agonists^[1]. Mechanistically, ATP and UTP can both mobilize Ca²⁺ through human P2Y11 receptor, but they recruit distinct signaling pathways^[2]. In immune biology, current evidence supports a role for P2Y11 in immune activation with cell type-specific effects^[3]. In disease models, P2RY11 variants associate with narcolepsy and altered ATP-induced cell death in T lymphocytes and NK cells^[4]. In rheumatoid arthritis-derived fibroblast-like synoviocytes, P2Y11R expression rises and NF340 suppresses IL-1β-induced TNF-α, IL-6, MMP expression, oxidative stress, and NFκB signaling^[5]. In lung fibroblasts, extracellular ATP or oxidative stress induces premature senescence through P2Y11R-linked ER Ca²⁺ release and mitochondrial ROS production^[6]. Compared with related isoforms, P2Y11 remains experimentally distinctive because rodents lack a murine P2ry11 orthologue and some antibodies, expression assays, agonists, and antagonists have specificity limitations^[3]. Therefore, P2Y11 receptor studies require human-relevant systems and carefully validated pharmacological tools^[3].