5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis

Yasunori Sakairi, Harry R. Jacobson, Thomas D. Noland, Jorge H. Capdevila, John R. Falck, Matthew D. Breyer

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


We examined the mechanism by which the cytochrome P-450 metabolite of arachidonate, 5,6-epoxyeicosatrienoic acid (5,6-EET), modulates electrogenic transport in the rabbit cortical collecting duct (CCD). 5,6-EET depolarized transepithelial voltage (VT) in a concentration-dependent manner with a maximal effect at 1 μM. None of the other EET regioisomers (8,9-, 11,12-, or 14,15-EET; all at 1 μM) affected VT. This action was also stereoselective, with 5(S),6(R)-EET producing a 2.5-fold greater effect on VT than 5(R),6(S)-EET (1 μM each). Like basolateral prostaglandin E2 (PGE2), both luminal and basolateral 5,6-EET increased cytosolic Ca2+ concentration ([Ca2+]i) in the rabbit CCD. Pretreatment with cyclooxygenase inhibitors (10 μM ibuprofen or 5 μM indomethacin) completely blocked both the [Ca2+]i increase and the change in VT. Neither 5,6-epoxy-PGE1 nor 5-hydroxy-PGI1, cyclooxygenase metabolites of 5,6-EET, affected VT. However, when added to primary cultures of rabbit CCDs, 5,6-EET stimulated endogenous PGE2 synthesis. We propose that 5,6-EET stimulates endogenous prostaglandin synthesis, which inhibits electrogenic ion transport in the CCD.

Original languageEnglish (US)
Pages (from-to)F931-F939
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number5 37-5
StatePublished - May 1995


  • 5,6-epoxyeicosatrienoic acid
  • Arachidonate
  • Cytochrome P-450
  • Kidney
  • Sodium

ASJC Scopus subject areas

  • Physiology


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