CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10pS chloride channel in the rat thick ascending limb | Zendy

Ruimin Gu | Zendy; Lei Yang | Zendy; Yunhong Zhang | Zendy; Lijun Wang | Zendy; Shumin Kong | Zendy; Chengbiao Zhang | Zendy; Yuanyuan Zhai | Zendy; Mingxiao Wang | Zendy; Peng Wu | Zendy; Liping Liu | Zendy; Feng Gu | Zendy; Jiye Zhang | Zendy; WenHui Wang | Zendy

Open Access

CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10pS chloride channel in the rat thick ascending limb

Author(s) -

Ruimin Gu,

Lei Yang,

Yunhong Zhang,

Lijun Wang,

Shumin Kong,

Chengbiao Zhang,

Yuanyuan Zhai,

Mingxiao Wang,

Peng Wu,

Liping Liu,

Feng Gu,

Jiye Zhang,

WenHui Wang

Publication year - 2009

Publication title -

kidney international

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.499

H-Index - 276

eISSN - 1523-1755

pISSN - 0085-2538

DOI - 10.1038/ki.2009.287

Subject(s) - arachidonic acid , chemistry , nordihydroguaiaretic acid , hydroxylation , biochemistry , cyclooxygenase , hydroxyeicosatetraenoic acid , lipoxygenase , metabolite , endocrinology , medicine , biology , enzyme

Metabolites of arachidonic acid influence sodium chloride (NaCl) transport in the thick ascending limb. Because a 10 pS Cl channel is the major type of chloride channel in the basolateral membrane of this nephron segment, we explored the effect of arachidonic acid on this channel in cell-attached patches. Addition of 5 micromol arachidonic acid significantly decreased channel activity (a product of channel number and open probability) while linoleic acid had no effect. To determine if this was mediated by acachidonic acid per se or by its metabolites, we measured channel activity in the presence of the cyclooxygenase inhibitor indomethacin, the selective lipoxygenase inhibitor nordihydroguaiaretic acid, and the cytochrome P-450 (CYP)-omega-hydroxylation inhibitor 17-octadecynoic acid. Neither cyclooxygenase nor lipoxygenase inhibition had an effect on basal chloride channel activity; further they failed to abolish the inhibitory effect of arachidonate on the 10 pS channel. However, inhibition of CYP-omega-hydroxylation completely abolished the effect of arachidonic acid. The similarity of the effects of 20-hydroxyeicosatetraenoic acid (20-HETE) and arachidonic acid suggests that the effect of arachidonic acid was mediated by CYP-omega-hydroxylation-dependent metabolites. We conclude that arachidonic acid inhibits the 10 pS chloride channel in the basolateral membrane of the medullary thick ascending limb, an effect mediated by the CYP-omega-hydroxylation-dependent metabolite 20-HETE.

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