P2Y6

P2Y6 is a purinergic G protein-coupled receptor that belongs to the P2Y family. It is encoded by the P2RY6 gene in humans and functions as a receptor for extracellular nucleotides, with UDP as its principal endogenous agonist. Upon activation, P2Y6 couples to Gq/11 proteins, triggering phospholipase Cβ activity, generation of inositol trisphosphate and diacylglycerol, and the release of calcium from intracellular stores.

The receptor’s signaling pathway leads to various Ca2+-dependent responses, including changes in secretion, metabolism, and cytoskeletal dynamics. In many cell types, P2Y6 activation modulates phagocytosis and inflammatory processes, linking tissue damage signals to microglial and macrophage responses.

Expression of P2Y6 is broad but remains particularly documented in the brain and immune system. In the central nervous system, it is found on neurons and glia, including microglia, where it participates in responses to injury. In the immune compartment, P2Y6 contributes to macrophage and microglial function and may influence cytokine production and cell motility.

Pharmacology and research tools include selective antagonists such as MRS 2578, which help delineate P2Y6-specific signaling in experimental systems. UDP’s role as an endogenous ligand makes P2Y6 a focus of interest for modulating neuroinflammation and tissue repair.

Clinical relevance is primarily in the context of inflammatory and neurodegenerative conditions, where P2Y6 signaling may influence microglial activity and phagocytosis. Ongoing research aims to clarify its therapeutic potential and its interaction with other purinergic receptors.