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 journalArticle

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Abstract

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)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume268
Issue number5 37-5
StatePublished - May 1995

Fingerprint

Ion Transport
Prostaglandins
Rabbits
Dinoprostone
Cyclooxygenase Inhibitors
5,6-epoxy-8,11,14-eicosatrienoic acid
Alprostadil
Ibuprofen
Prostaglandin-Endoperoxide Synthases
Indomethacin
Cytochrome P-450 Enzyme System

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis. / Sakairi, Yasunori; Jacobson, Harry R.; Noland, Thomas D.; Capdevila, Jorge H.; Falck, John R.; Breyer, Matthew D.

In: American Journal of Physiology - Renal Fluid and Electrolyte Physiology, Vol. 268, No. 5 37-5, 05.1995.

Research output: Contribution to journalArticle

Sakairi, Yasunori ; Jacobson, Harry R. ; Noland, Thomas D. ; Capdevila, Jorge H. ; Falck, John R. ; Breyer, Matthew D. / 5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis. In: American Journal of Physiology - Renal Fluid and Electrolyte Physiology. 1995 ; Vol. 268, No. 5 37-5.
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