LPAR3

Lysophosphatidic acid receptor 3 (LPAR3) is a G protein-coupled receptor that mediates calcium signaling in epithelial and neuronal cells^[1][2]. Mechanistically, LPAR3 activation stimulates intracellular calcium flux via Gq/PLC pathways, regulating chloride secretion at the ocular surface and modulating erythropoietic processes in hematopoietic stem cells^[1][2]. In vivo, LPAR3 knockout models in zebrafish exhibit behavioral alterations, including disrupted circadian locomotor activity, reduced aggression, and impaired memory, demonstrating its involvement in neurobehavioral regulation^[2]. In disease models, LPAR3 contributes to ocular surface homeostasis, including Cl^- transport in corneal epithelial cells, suggesting potential roles in dry eye and neuropathic pain^[1]. Compared with related LPA receptors such as LPAR1 and LPAR5, LPAR3 exhibits distinct tissue expression patterns in ocular, hematopoietic, and neural cells, as well as selective coupling to calcium-dependent signaling rather than exclusively PI3K/AKT or cAMP pathways^[1][2][3]. Pharmacologically, LPAR3-selective agonists like 2S-OMPT enhance calcium-dependent chloride secretion in human corneal epithelial cells, providing experimental tools for studying epithelial transport and ocular surface disease mechanisms^[1]. Dual LPAR1/LPAR3 antagonists can mitigate LPC/LPA-induced visceral hypersensitivity, highlighting LPAR3 as a target for pain modulation^[3]. Collectively, these findings define LPAR3 as a versatile receptor with functional specificity in calcium signaling, neurobehavior, epithelial transport, and sensory modulation.