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Arachidonic acid (AA) stimulates Ca2+‐activated big conductance K (BK) channel in the cortical collecting duct (CCD) via cytochrome P450 (CYP) epoxygenase‐dependent metabolic pathways.
Author(s) -
Sun Peng,
Wang Wenhui
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.934.14
Subject(s) - epoxygenase , bk channel , chemistry , arachidonic acid , cytochrome p450 , metabolite , epoxyeicosatrienoic acid , cyclooxygenase , endocrinology , medicine , biochemistry , metabolism , membrane potential , enzyme , biology
We used the patch‐clamp technique to study the effect of AA on BK channels in principal cell of the CCD in rat kidney. The dose‐response curve of the AA effect on BK yields that 10 μM AA caused a maximal stimulation of BK and increased NPo from 0.0004 to 0.45. The effect of AA on BK was specific because application of 11,14,17‐eicosatrienoic acid had no effect on BK. To determine the metabolic pathway by which AA‐induced stimulation of BK, we examined the effect of AA in the presence of indomethcin, DDMS and MS‐PPOH. Inhibition of either cyclooxygenase with indomethacin or CYP‐monooxidase with DDMS failed to abolish the stimulatory effect of AA on BK. In contrast, AA‐induced activation of BK was absent in the presence of MS‐PPOH, an inhibitor of CYP epoxygenase. The notion that the stimulative effect of AA on BK is mediated by CYP epoxygenase‐dependent metabolites is also supported by the observation that application of 100 nM 11,12‐epoxyeicosatrienoic acid (EET) mimicked the effect of AA. In contrast, addition of either 8,9‐, or 14,15‐EET failed to stimulate BK. Moreover, application of 11,12‐EET was still able to activate BK in the presence of MS‐PPOH. This suggests that 11,12‐EET is a mediator for the AA‐induced activation of BK. We conclude that AA activates BK activity in the CCD and that the effect of AA is mediated by a CYP epoxygenase‐dependent metabolite, 11,12‐EET.