TY - JOUR
T1 - 5,6-EET inhibits ion transport in collecting duct by stimulating endogenous prostaglandin synthesis
AU - Sakairi, Yasunori
AU - Jacobson, Harry R.
AU - Noland, Thomas D.
AU - Capdevila, Jorge H.
AU - Falck, John R.
AU - Breyer, Matthew D.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - 5,6-epoxyeicosatrienoic acid
KW - arachidonate
KW - cytochrome P-450
KW - kidney
KW - sodium
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U2 - 10.1152/ajprenal.1995.268.5.f931
DO - 10.1152/ajprenal.1995.268.5.f931
M3 - Article
C2 - 7771521
AN - SCOPUS:0029059860
VL - 268
SP - F931-F939
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 5 37-5
ER -