Y. Sakairi et al., 5,6-EET INHIBITS ION-TRANSPORT IN COLLECTING DUCT BY STIMULATING ENDOGENOUS PROSTAGLANDIN SYNTHESIS, American journal of physiology. Renal, fluid and electrolyte physiology, 37(5), 1995, pp. 931-939
We examined the mechanism by which the cytochrome P-450 metabolite of
arachidonate, 5,6-epoxyeicosatrienoic acid (5,6-EET), modulates electr
ogenic transport in the rabbit cortical collecting duct (CCD). 5,6-EET
depolarized transepithelial voltage (V-T) in a concentration-dependen
t manner with a maximal effect at 1 mu M. None of the other EET regioi
somers (8,9-, 11,12-, or 14,15-EET; all at 1 mu M) affected V-T. This
action was also stereoselective, with 5(S),G(R)-EET producing a 2.5-fo
ld greater effect on V-T than 5(R),6(S)-EET (1 mu M each). Like basola
teral prostaglandin E(2) (PGE(2)), both luminal and basolateral 5,6-EE
T increased cytosolic Ca2+ concentration ([Ca2+](i)) in the rabbit CCD
. Pretreatment with cyclooxygenase inhibitors (10 mu M ibuprofen or 5
mu M indomethacin) completely blocked both the [Ca2+]i increase and th
e change in V-T Neither 5,B-epoxy-PGE(1) nor 5-hydroxy-PGI(1), cycloox
ygenase metabolites of 5,6-EET, affected V-T. However, when added to p
rimary cultures of rabbit CCDs, 5,6-EET stimulated endogenous PGE(2) s
ynthesis. We propose that 5,6-EET stimulates endogenous prostaglandin
synthesis, which inhibits electrogenic ion transport in the CCD.