P2Y purinoceptor family (P2YR)

The P2Y purinoceptor family comprises eight distinct G protein-coupled receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14) that respond to extracellular nucleotides like ATP, ADP, UTP, and UDP [1]. These receptors are categorized into two subgroups based on their G protein coupling: the P2Y1-like group which primarily couples to Gq to activate phospholipase C, and the P2Y12-like group which couples to Gi to inhibit adenylyl cyclase [2]. They are ubiquitously expressed and mediate a wide array of physiological functions, including platelet aggregation, smooth muscle contraction, and immune cell activation [3]. Clinically, the P2Y12 receptor is the most prominent target, with antagonists like clopidogrel and ticagrelor serving as standard-of-care antiplatelet agents for cardiovascular protection [4]. Other family members are being explored for treating conditions such as dry eye syndrome, where P2Y2 agonists stimulate fluid secretion, and inflammatory diseases [5]. Understanding the structural diversity and specific ligand preferences of these receptors remains crucial for developing selective therapeutic agents with minimized side effects [1, 5].

Other names

P2Y receptorsPurinergic P2Y receptorsMetabotropic purinoceptorsG protein-coupled purinergic receptors

Drugs targeting the P2Y purinoceptor family function as either agonists or antagonists to modulate downstream signaling. P2Y12 antagonists (e.g., clopidogrel, ticagrelor) block ADP-induced platelet activation by preventing Gi-mediated inhibition of adenylyl cyclase, thereby maintaining high cAMP levels and inhibiting aggregation [3, 4]. Conversely, P2Y2 agonists (e.g., diquafosol) activate Gq-coupled pathways to increase intracellular calcium and stimulate mucin and fluid secretion in epithelial tissues [5].