P2Y purinoceptor 2 (P2Y2) (P2Y2)

P2Y purinoceptor 2 (P2Y2) is a G protein-coupled receptor (GPCR) that is uniquely activated by both extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) [UniProt: P35344]. It is widely expressed in various tissues, including the airway epithelia, ocular surface, and vascular endothelium, where it primarily couples to the Gq/11 protein to trigger the phospholipase C (PLC) signaling pathway and subsequent intracellular calcium mobilization [IUPHAR: P2Y2 receptor]. This signaling cascade regulates critical physiological processes such as chloride ion secretion, mucin production, and ciliary beat frequency, making it a key regulator of mucosal surface hydration and clearance [PubMed: 25633331]. In clinical practice, P2Y2 is a validated therapeutic target for dry eye syndrome, where agonists like diquafosol are employed to enhance the natural components of the tear film [PubMed: 22103801]. Beyond ocular health, the receptor is implicated in inflammatory responses, wound healing, and the pathophysiology of cystic fibrosis and certain cancers, though its role in promoting cell migration and inflammation presents challenges for systemic therapeutic applications [PubMed: 28843415].

Other names

P2RY2Purinergic receptor P2Y2P2U receptorATP receptorP2U1Purinoceptor P2Y2

Agonism of the P2Y2 receptor activates the Gq/PLC/IP3 signaling pathway, leading to increased intracellular calcium levels which stimulate apical chloride channels and trigger the release of mucins from goblet cells [PubMed: 22103801].