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

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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 (V(T)) 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 V(T). This action was also stereoselective, with 5(S),6(R)-EET producing a 2.5-fold greater effect on V(T) 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 V(T). 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
Volume268
Issue number5 37-5
StatePublished - Jan 1 1995

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Keywords

  • 5,6-epoxyeicosatrienoic acid
  • arachidonate
  • cytochrome P-450
  • kidney
  • sodium

ASJC Scopus subject areas

  • Physiology

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