P2Y4

P2Y4 is a member of the P2Y family of purinergic G protein-coupled receptors. In humans, the receptor is encoded by the P2RY4 gene. P2Y4 is activated by nucleotide signals, with UTP serving as its principal agonist in many species. The receptor contributes to cellular responses to extracellular nucleotides in diverse tissues.

Mechanistically, P2Y4 predominantly couples to Gq/11 family proteins. Activation of these G proteins stimulates phospholipase C beta, leading to inositol trisphosphate production, release of calcium from intracellular stores, and subsequent activation of protein kinase C. In some cellular contexts, the receptor may couple to additional G proteins, giving rise to signaling that can modulate cAMP levels or other pathways, depending on the cell type and environment.

Pharmacology of P2Y4 centers on nucleotide ligands. UTP is the primary activator, with species-dependent responsiveness to UDP and related nucleotides. The receptor’s exact ligand selectivity and pharmacological profile have been investigated in various in vitro systems, contributing to the understanding of its role in purinergic signaling.

Distribution and function of P2Y4 have been studied in several tissues. It is expressed in components of the nervous system and in peripheral tissues including airway epithelia and smooth muscle, where it participates in Ca2+-dependent signaling cascades. Through these pathways, P2Y4 can influence processes such as epithelial ion transport, neurotransmission, and vascular or smooth muscle function, reflecting the broader role of purinergic signaling in physiology.

Further study continues to clarify species differences, tissue-specific signaling, and potential therapeutic implications of P2Y4 modulation.