ArticleThe Journal of pharmacology and experimental therapeutics2014
The biological actions of 11,12-epoxyeicosatrienoic acid in endothelial cells are specific to the R/S-enantiomer and require the G(s) protein.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- The Hunt for the Putative Epoxyeicosatrienoic Acid Receptor.ACS chemical biology · 2025Review
- Article
- Pathophysiological Involvement of Mast Cells and the Lipid Mediators in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2023Review
- The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms.Prostaglandins & other lipid mediators · 2022Article
- Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.Signal transduction and targeted therapy · 2021Review
- Review
- CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design.Pharmacology & therapeutics · 2020Review
- Soluble epoxide hydrolase as a therapeutic target for obesity-induced disorders: roles of gut barrier function involved.Prostaglandins, leukotrienes, and essential fatty acids · 2020Review
- Cytochrome P450 monooxygenase/soluble epoxide hydrolase-mediated eicosanoid pathway in colorectal cancer and obesity-associated colorectal cancer.Oncoscience · 2019Article
- Endothelial Transient Receptor Potential Channels and Vascular Remodeling: Extracellular CaFrontiers in physiology · 2019Review
- Chiral lipidomics of monoepoxy and monohydroxy metabolites derived from long-chain polyunsaturated fatty acids.Journal of lipid research · 2019Article
- New Lipid Mediators in Retinal Angiogenesis and Retinopathy.Frontiers in pharmacology · 2019Review
- Oxidized Lipids in Persistent Pain States.Frontiers in pharmacology · 2019Review
- Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- GPR40 is a low-affinity epoxyeicosatrienoic acid receptor in vascular cells.The Journal of biological chemistry · 2018Article
- Metabolic/inflammatory/vascular comorbidity in psychiatric disorders; soluble epoxide hydrolase (sEH) as a possible new target.Neuroscience and biobehavioral reviews · 2018Review
- Epoxide hydrolase 1 (EPHX1) hydrolyzes epoxyeicosanoids and impairs cardiac recovery after ischemia.The Journal of biological chemistry · 2018Article
- TRP Channels in Angiogenesis and Other Endothelial Functions.Frontiers in physiology · 2018Review
- Orally Active Epoxyeicosatrienoic Acid Analogs.Journal of cardiovascular pharmacology · 2017Review
- 11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature.Autonomic & autacoid pharmacology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Cytochrome P450-derived epoxides of arachidonic acid [i.e., the epoxyeicosatrienoic acids (EETs)] are important lipid signaling molecules involved in the regulation of vascular tone and angiogenesis. Because many actions of 11,12-cis-epoxyeicosatrienoic acid (EET) are dependent on the activation of protein kinase A (PKA), the existence of a cell-surface G(s)-coupled receptor has been postulated. To assess whether the responses of endothelial cells to 11,12-EET are enantiomer specific and linked to a potential G protein-coupled receptor, we assessed 11,12-EET-induced, PKA-dependent translocation of transient receptor potential (TRP) C6 channels, as well as angiogenesis. In primary cultures of human endothelial cells, (±)-11,12-EET led to the rapid (30 seconds) translocation a TRPC6-V5 fusion protein, an effect reproduced by 11(R),12(S)-EET, but not by 11(S),12(R)-EET or (±)-14,15-EET. Similarly, endothelial cell migration and tube formation were stimulated by (±)-11,12-EET and 11(R),12(S)-EET, whereas 11(S),12(R)-EET and 11,12-dihydroxyeicosatrienoic acid were without effect. The effects of (±)-11,12-EET on TRP channel translocation and angiogenesis were sensitive to EET antagonists, and TRP channel trafficking was also prevented by a PKA inhibitor. The small interfering RNA-mediated downregulation of G(s) in endothelial cells had no significant effect on responses stimulated by vascular endothelial growth or a PKA activator but abolished responses to (±)-11,12-EET. The downregulation of G(q)/11 failed to prevent 11,12-EET-induced TRPC6 channel translocation or the formation of capillary-like structures. Taken together, our results suggest that a G(s)-coupled receptor in the endothelial cell membrane responds to 11(R),12(S)-EET and mediates the PKA-dependent translocation and activation of TRPC6 channels, as well as angiogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.