5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis
Sakairi, Y.; Jacobson, H.R.; Noland, T.D.; Capdevila, J.H.; Falck, J.R.; Breyer, M.D.
American Journal of Physiology 268(5 Pt 2): F931-F939
1995
ISSN/ISBN: 0002-9513 PMID: 7771521 Document Number: 454173
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 mu-M. None of the other EET regioisomers (8,9-, 11,12-, or 14,15-EET; all at 1 mu-M) 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 mu-M each). Like basolateral prostaglandin E-2 (PGE-2), both luminal and basolateral 5,6-EET increased cytosolic Ca-2+ concentration ((Ca-2+)-i) in the rabbit CCD. Pretreatment with cyclooxygenase inhibitors (10 mu-M ibuprofen or 5 mu-M indomethacin) completely blocked both the (Ca-2+)-i increase and the change in V-T. Neither 5,6-epoxy-PGE-1 nor 5-hydroxy-PGI-1, cyclooxygenase metabolites of 5,6-EET, affected V-T. However, when added to primary cultures of rabbit CCDs, 5,6-EET stimulated endogenous PGE-2 synthesis. We propose that 5,6-EET stimulates endogenous prostaglandin synthesis, which inhibits electrogenic ion transport in the CCD.