5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis.
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 microM. None of the other EET regioisomers (8,9-, 11,12-, or 14,15-EET; all at 1 microM) 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 microM 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 microM ibuprofen or 5 microM 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.
Sakairi
Y
Y
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
Jacobson
H R
HR
Noland
T D
TD
Capdevila
J H
JH
Falck
J R
JR
Breyer
M D
MD
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis; D004594:Electrophysiology; D004848:Epithelium / Q000502:physiology; D005260:Female; D007477:Ions; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D015398:Signal Transduction; D013237:Stereoisomerism
D007477:Ions; D011453:Prostaglandins; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; D011451:Prostaglandin-Endoperoxide Synthases; D015126:8,11,14-Eicosatrienoic Acid; D015232:Dinoprostone