GPR40 is a low-affinity epoxyeicosatrienoic acid receptor in vascular cells

The Journal of Biological Chemistry
Sang-Kyu ParkW B Campbell

Abstract

Endothelium-derived epoxyeicosatrienoic acids (EETs) have numerous vascular activities mediated by G protein-coupled receptors. Long-chain free fatty acids and EETs activate GPR40, prompting us to investigate the role of GPR40 in some vascular EET activities. 14,15-EET, 11,12-EET, arachidonic acid, and the GPR40 agonist GW9508 increase intracellular calcium concentrations in human GPR40-overexpressing HEK293 cells (EC50 = 0.58 ± 0.08 μm, 0.91 ± 0.08 μm, 3.9 ± 0.06 μm, and 19 ± 0.37 nm, respectively). EETs with cis- and trans-epoxides had similar activities, whereas substitution of a thiirane sulfur for the epoxide oxygen decreased the activities. 8,9-EET, 5,6-EET, and the epoxide hydrolysis products 11,12- and 14,15-dihydroxyeicosatrienoic acids were less active than 11,12-EET. The GPR40 antagonist GW1100 and siRNA-mediated GPR40 silencing blocked the EET- and GW9508-induced calcium increases. EETs are weak GPR120 agonists. GPR40 expression was detected in human and bovine endothelial cells (ECs), smooth muscle cells, and arteries. 11,12-EET concentration-dependently relaxed preconstricted coronary arteries; however, these relaxations were not altered by GW1100. In human ECs, 11,12-EET increased MAP kinase (MAPK)-mediated ERK p...Continue Reading

References

Jan 1, 1990·Methods in Enzymology·J R FalckJ Capdevila
Jan 1, 1988·The American Journal of Physiology·G E RevtyakW B Campbell
Aug 1, 1988·The American Journal of Physiology·G E RevtyakW B Campbell
Sep 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·J CapdevilaR W Estabrook
Feb 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·J CapdevilaR W Estabrook
Mar 1, 1993·The Journal of Physiology·S M Marchenko, S O Sage
Oct 16, 1999·Nature·B FisslthalerR Busse
Jan 29, 2000·Histochemistry and Cell Biology·M J van Kempen, H J Jongsma
Aug 18, 2001·Molecular and Cellular Biology·J K ChenR C Harris
Oct 13, 2001·Circulation Research·S T Davidge
Oct 18, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Gary D SnyderArthur A Spector
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·J R FalckWilliam B Campbell
Dec 17, 2002·The Journal of Physiology·Kathryn M GauthierNancy J Rusch
Dec 24, 2002·The Journal of Biological Chemistry·Celia P BriscoeAlison I Muir
Sep 25, 2003·Physiological Reviews·Juan C SaezEric C Beyer
Jan 13, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Florian KrötzUlrich Pohl
Dec 1, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·U Ruth MichaelisIngrid Fleming
May 27, 2005·The Journal of Biological Chemistry·Ambra PozziJorge H Capdevila
Aug 6, 2005·Biochemical and Biophysical Research Communications·Hagit ShapiroMichael D Walker
Sep 7, 2005·American Journal of Physiology. Heart and Circulatory Physiology·William B CampbellKathryn M Gauthier
Nov 1, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Brandon T LarsenDavid D Gutterman
Nov 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yi LiuJohn Y-J Shyy
Nov 5, 2005·Circulation Research·Scott EarleyJoseph E Brayden
Apr 18, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Anuradha DhanasekaranMeetha Medhora
Nov 15, 2006·Molecular and Cellular Endocrinology·Susanne SchnellChristof Schöfl
Dec 8, 2006·Trends in Pharmacological Sciences·Brandon T LarsenDavid D Gutterman
Dec 14, 2006·Prostaglandins & Other Lipid Mediators·Ingrid Fleming
Jan 4, 2007·Hypertension·William B Campbell, John R Falck
Feb 27, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Shilin YangDarryl C Zeldin
Jun 9, 2007·Journal of Molecular Endocrinology·Ying ZhangHua Cheng
Sep 18, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Ingrid FlemingRudi Busse
May 1, 2008·The Journal of Pharmacology and Experimental Therapeutics·Houli JiangJohn C McGiff

❮ Previous
Next ❯

Citations

Jul 17, 2019·Clinical Science·Jean-François ThibodeauLyne Gagnon
Sep 6, 2019·Physiological Reviews·Ikuo KimuraMiki Igarashi
May 27, 2020·Journal of Cellular Physiology·Xiao-Qin LuoCha-Xiang Guan
Jul 4, 2018·International Journal of Molecular Sciences·Theresa AliwargaRheem A Totah
Sep 14, 2019·International Journal of Molecular Sciences·Shashank ShekharFan Fan
Aug 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jamie L LahvicLeonard I Zon
Sep 29, 2020·Frontiers in Pharmacology·Paige G SmithJocelyn C Reader
Jun 18, 2020·Antioxidants·Mong-Heng WangMohamed Al-Shabrawey
Nov 5, 2019·Frontiers in Pharmacology·Tabea Osthues, Marco Sisignano
Jul 25, 2019·Frontiers in Pharmacology·Ingrid Fleming
Sep 3, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Karen M WagnerBruce D Hammock
Oct 11, 2020·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Jianan ZhangGuodong Zhang
May 16, 2019·Free Radical Biology & Medicine·Cécile GladineNils Helge Schebb
Nov 14, 2020·International Journal of Molecular Sciences·Ken YasukawaTakehiko Yokomizo
May 28, 2021·Endocrinology·Gage M Stuttgen, Daisy Sahoo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.