P2Y purinoceptor 4 (P2Y4) (P2Y4)

The P2Y purinoceptor 4 (P2Y4) is a G protein-coupled receptor (GPCR) belonging to the P2Y family, specifically the P2Y1-like subfamily. In humans, P2Y4 is highly selective for uridine triphosphate (UTP) over adenosine triphosphate (ATP), whereas in rodents, it is activated by both nucleotides (UniProt: P51441). Upon activation, P2Y4 couples to Gq/11 proteins, stimulating phospholipase C and increasing intracellular calcium levels (IUPHAR/BPS Guide to Pharmacology). This receptor is prominently expressed in epithelial cells of the lung and intestine, where it regulates chloride secretion and fluid transport, making it a potential therapeutic target for cystic fibrosis and secretory diarrhea (PubMed: 10449511). Beyond epithelial transport, P2Y4 is involved in cardiac function, neuroprotection, and inflammatory signaling. Therapeutic development targeting P2Y4 has faced challenges due to the high degree of homology among P2Y receptor subtypes and significant species-specific pharmacological profiles (PubMed: 24764307).

Other names

P2RY4Uridine nucleotide receptorUNRPurinergic receptor P2Y4P2Y receptor family member 4

Agonism of the P2Y4 receptor activates the Gq/11 protein pathway, leading to phospholipase C (PLC) activation, which results in the generation of inositol trisphosphate (IP3) and diacylglycerol (DAG), ultimately triggering intracellular calcium mobilization and downstream signaling cascades (IUPHAR/BPS Guide to Pharmacology).