LTE4receptor

LTE4 receptor refers to the cellular receptor that mediates responses to leukotriene E4 (LTE4), a product of arachidonic acid metabolism involved in inflammatory signaling. The best-characterized receptor for LTE4 in humans is GPR99, a G protein-coupled receptor encoded by the GPR99 gene. In some historical and preclinical literature, GPR99 is also referred to as Oxoglutarate receptor 1 (OXGR1); however, the naming can vary across studies. LTE4 signaling through GPR99 is distinct in part from signaling by the classical cysteinyl leukotriene receptors CysLT1R and CysLT2R, which primarily recognize LTC4 and LTD4 and show only limited responsiveness to LTE4 in some contexts.

Discovery and naming of the LTE4 receptor reflect a shift in understanding leukotriene signaling. While CysLT1R and CysLT2R have long been known to mediate cysteinyl leukotriene effects, LTE4 can provoke biological responses that are not fully accounted for by these receptors. GPR99 emerged as a receptor with higher sensitivity to LTE4, highlighting a separate pathway for LTE4-driven inflammation and bronchoconstriction.

Signaling and pharmacology associated with the LTE4 receptor involve coupling of the receptor to G proteins, leading to intracellular calcium mobilization and modulation of other second messenger systems in certain cell types. LTE4 acts as an agonist at this receptor, though ligand selectivity and signaling details can vary with cell type and context. Antagonists or modulators of GPR99 are under investigation as potential therapeutic strategies to reduce LTE4-mediated inflammation in airway diseases.

Expression patterns include airway epithelium, smooth muscle, and various immune cells such as mast cells and eosinophils, aligning with roles in asthma and related inflammatory conditions. The LTE4 receptor is considered a potential target for improving control of LTE4-driven pathology, including some forms of aspirin-exacerbated respiratory disease, where LTE4 signaling contributes to symptoms despite CysLT1R antagonism.