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Arachidonic acid (AA) inhibits basolateral K channels in the cortical collecting duct (CCD) via cytochrome P450 (CYP) epoxygenase‐dependent metabolic pathways
Author(s) -
Wang Zhijian,
Wei Yuan,
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.1201.3
Subject(s) - epoxygenase , chemistry , arachidonic acid , cytochrome p450 , inhibitory postsynaptic potential , epoxyeicosatrienoic acid , metabolite , patch clamp , stereochemistry , biophysics , biochemistry , endocrinology , enzyme , biology , receptor
We used the patch‐clamp technique to study the effect of AA on basolateral 18 pS K channels in principal cell of the CCD of the rat kidney. Application of AA inhibited the 18 pS K channels. The effect of AA on the 18 pS K channel was specific because application of 11,14,17‐eicosatrienoic acid had no effect. Also, the inhibitory effect of AA on the 18 pS K channels was abolished by blocking CYP epoxygenase with MS‐PPOH but was not affected by DDMS, an inhibitor of CYP monoxygenase. The notion that the inhibitory effect of AA was mediated by CYP epoxygenase‐dependent metabolites was also supported by the observation that application of 100 nM 11,12‐epoxyeicosatrienoic acid (EET) mimicked the effect of AA and inhibited the basolateral 18 pS K channels. In contrast, addition of either 8,9‐, or 14,15‐EET failed to inhibit the 18 pS K channels. Moreover, application of 11,12‐EET was still able to inhibit the 18 pS K channels in the presence of MS‐PPOH. This suggests that 11,12‐EET is a mediator for the AA‐induced inhibition of the 18 pS K channels. We conclude that AA inhibits basolateral 18 pS K channels in the CCD and that the effect of AA is mediated by a CYP epoxygenase‐dependent metabolite, 11,12‐EET.