P2Y2

P2Y2 receptor is a purinergic G protein-coupled receptor in the P2Y family. In humans it is encoded by the P2RY2 gene. The receptor is activated by extracellular nucleotides, notably ATP and UTP. Upon activation, P2Y2 couples predominantly to Gq/11 proteins, triggering phospholipase Cβ, generating inositol trisphosphate and diacylglycerol, and raising intracellular calcium. Depending on cellular context, signaling can also involve other pathways in certain cell types.

Expression of P2Y2 is widespread, with high levels in epithelial and endothelial cells, including the airways, ocular tissues, kidney, and some immune cells. Functionally, P2Y2 activation promotes chloride secretion and water movement in epithelia, contributing to mucosal hydration and tear film production. It also supports mucociliary clearance in airways and can influence ion transport, cell migration, and wound healing. In the immune system, P2Y2 signaling can affect leukocyte chemotaxis and cytokine release.

Clinical relevance and therapeutic targeting have focused on its role in mucosal hydration. P2Y2 receptor agonists have been explored for dry eye disease; diquafosol tetrasodium is a clinically used P2Y2 agonist in some regions. In cystic fibrosis research, P2Y2 agonists were investigated as a means to stimulate calcium-activated chloride secretion independent of CFTR, though clinical outcomes have been variable. As a GPCR, P2Y2 features the seven-transmembrane architecture typical of this receptor family.