P2Y purinoceptor 14 (P2Y14)

P2Y purinoceptor 14 (P2Y14) is a G protein-coupled receptor (GPCR) that belongs to the P2Y receptor family, specifically the P2Y12-like subgroup (UniProt, Q15391). Unlike other P2Y receptors that typically respond to nucleotides like ATP or ADP, P2Y14 is uniquely activated by UDP-sugars, such as UDP-glucose and UDP-galactose (IUPHAR/BPS Guide to Pharmacology). It is primarily coupled to Gi/o proteins, leading to the inhibition of adenylyl cyclase and the activation of downstream signaling pathways involved in chemotaxis and cytokine production (Abbracchio et al., 2006). P2Y14 is widely expressed in the immune system, including neutrophils, eosinophils, and mast cells, as well as in the lungs, kidneys, and central nervous system (PubMed, PMID: 22519244). It plays a significant role in mediating inflammatory responses, particularly in conditions like asthma, chronic obstructive pulmonary disease (COPD), and gouty arthritis (Muller et al., 2017). Research indicates that P2Y14 acts as a sensor for tissue damage, as UDP-glucose is released into the extracellular space during cell injury or stress (Jacobson et al., 2012). Consequently, P2Y14 has emerged as a promising therapeutic target for inflammatory and metabolic diseases. Small molecule antagonists, such as PPTN, have demonstrated efficacy in preclinical models by reducing leukocyte recruitment and pro-inflammatory signaling (PubChem, CID 11533340).

Other names

P2RY14GPR105UDP-glucose receptorG-protein coupled receptor 105Purinergic receptor P2Y14

Antagonism of the P2Y14 receptor inhibits Gi protein-mediated signaling, which prevents the inhibition of adenylyl cyclase and subsequently reduces the recruitment and activation of inflammatory cells such as neutrophils and eosinophils.