The role of P2Y₆ receptor in the pathogenesis of cardiovascular and inflammatory diseases

The purinergic receptor P2Y₆ receptor (P2Y₆R) is a member of the G protein-coupled receptors (GPCR) family. P2Y₆R is widely expressed in various cell types and plays a critical role in physiological processes, where it is activated by extracellular uridine diphosphate (UDP) and mobilizes Ca²⁺ via the G_αq/11 protein pathway. We have recently discovered the pathophysiological role of P2Y₆R in cardiovascular and inflammatory diseases, including inflammatory bowel disease and non-alcoholic fatty liver disease. Furthermore, we uncovered the redox-dependent internalization of P2Y₆R. In this review, we provide a comprehensive overview of the pathophysiological activity of P2Y₆R in cardiovascular and inflammatory diseases. Additionally, we discuss the concept of atypical internalization control of GPCRs, which may be applied in the prevention and treatment of intestinal inflammation and cardiovascular remodeling.