Epoxyeicosatrienoic acid receptor (EET receptor)

The Epoxyeicosatrienoic acid receptor (EET receptor) is a cell-surface receptor that mediates the diverse physiological effects of epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid produced by cytochrome P450 epoxygenases. Although a specific high-affinity receptor has been the subject of intense research for decades, it has not yet been definitively identified as a single protein; however, G protein-coupled receptors (GPCRs) such as GPR40 (FFAR1) and GPR120 (FFAR4) have been characterized as low-affinity mediators of EET signaling. The receptor is widely expressed in the cardiovascular system, particularly in endothelial and smooth muscle cells, as well as in the kidneys and pancreas. Activation of the EET receptor typically leads to vasodilation, anti-inflammatory responses, and cardioprotection, often through the activation of large-conductance calcium-activated potassium (BKCa) channels and the inhibition of NF-κB signaling. In clinical contexts, the EET receptor pathway is a target for treating hypertension, heart failure, and inflammatory diseases, with therapeutic strategies focusing on EET mimetics or inhibitors of soluble epoxide hydrolase (sEH) to increase endogenous EET levels. Despite its protective roles, there are significant safety concerns regarding the potential for EET receptor activation to stimulate angiogenesis and promote the growth and metastasis of certain tumors.

Other names

EET receptorPutative epoxyeicosatrienoic acid receptor14,15-EET receptor11,12-EET receptorGPR40 (low-affinity mediator)Free fatty acid receptor 1 (FFAR1)GPR120 (low-affinity mediator)Free fatty acid receptor 4 (FFAR4)

Agonism of the receptor to induce vasodilation and anti-inflammatory effects; Antagonism to block EET-mediated pathological processes such as tumor growth.