Functional screening for G protein-coupled receptor targets of 14,15-epoxyeicosatrienoic acid

Xuehong Liu, Zu yuan Qian, Fuchun Xie, Wei Fan, Jonathan W. Nelson, Xiangshu Xiao, Sanjiv Kaul, Anthony Barnes, Nabil Alkayed

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Epoxyeicosatrienoic acids (EETs) are potent vasodilators that play important roles in cardiovascular physiology and disease, yet the molecular mechanisms underlying the biological actions of EETs are not fully understood. Multiple lines of evidence suggest that the actions of EETs are in part mediated via G protein-coupled receptor (GPCR) signaling, but the identity of such a receptor has remained elusive. We sought to identify 14,15-EET-responsive GPCRs. A set of 105 clones were expressed in Xenopus oocyte and screened for their ability to activate cAMP-dependent chloride current. Several receptors responded to micromolar concentrations of 14,15-EET, with the top five being prostaglandin receptor subtypes (PTGER2, PTGER4, PTGFR, PTGDR, PTGER3IV). Overall, our results indicate that multiple low-affinity 14,15-EET GPCRs are capable of increasing cAMP levels following 14,15-EET stimulation, highlighting the potential for cross-talk between prostanoid and other ecosanoid GPCRs. Our data also indicate that none of the 105 GPCRs screened met our criteria for a high-affinity receptor for 14,15-EET.

Original languageEnglish (US)
JournalProstaglandins and Other Lipid Mediators
DOIs
StateAccepted/In press - Apr 28 2016

Keywords

  • CFTR
  • EET
  • Epoxyeicosatrienoic acid
  • GPCR
  • Prostaglandin E
  • Vasodilation

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Pharmacology
  • Cell Biology

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