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

Rui Min Gu; Lei Yang; Yunhong Zhang; Lijun Wang; Shumin Kong; Chengbiao Zhang; Yuanyuan Zhai; Mingxiao Wang; Peng Wu; Liping Liu; Feng Gu; Jiye Zhang; Wen Hui Wang

doi:10.1038/ki.2009.287

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

Rui Min Gu, Lei Yang, Yunhong Zhang, Lijun Wang, Shumin Kong, Chengbiao Zhang, Yuanyuan Zhai, Mingxiao Wang, Peng Wu, Liping Liu, Feng Gu, Jiye Zhang, Wen Hui Wang

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

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 mol 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)- 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- 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- 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- hydroxylation-dependent metabolite 20-HETE.

Original language	English
Pages (from-to)	849-856
Number of pages	8
Journal	Kidney International
Volume	76
Issue number	8
DOIs	https://doi.org/10.1038/ki.2009.287
State	Published - Oct 2009
Externally published	Yes

Keywords

20-HETE
CYP-o-hydroxylation
Cl transport
Cyclooxygenase

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10.1038/ki.2009.287

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@article{d0bd5229cf5b4bf4b10f71edfa5528b5,

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

abstract = "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 mol 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)- 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- 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- 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- hydroxylation-dependent metabolite 20-HETE.",

keywords = "20-HETE, CYP-o-hydroxylation, Cl transport, Cyclooxygenase",

author = "Gu, {Rui Min} and Lei Yang and Yunhong Zhang and Lijun Wang and Shumin Kong and Chengbiao Zhang and Yuanyuan Zhai and Mingxiao Wang and Peng Wu and Liping Liu and Feng Gu and Jiye Zhang and Wang, {Wen Hui}",

note = "Funding Information: This work was supported by National Nature Science Foundation of China no. 30570673 (R-MG), no. 30770800 (R-MG), the Research Fund of High Education for Doctoral Program no. 20040226 (R-MG), Youth Science Foundation of Medical Basic Subjects of Harbin Medical University, no. 060035 (LY) and NIH HL34300 (W-HW).",

year = "2009",

month = oct,

doi = "10.1038/ki.2009.287",

language = "English",

volume = "76",

pages = "849--856",

journal = "Kidney International",

issn = "0085-2538",

publisher = "Elsevier Inc.",

number = "8",

}

TY - JOUR

T1 - CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10 pS chloride channel in the rat thick ascending limb

AU - Gu, Rui Min

AU - Yang, Lei

AU - Zhang, Yunhong

AU - Wang, Lijun

AU - Kong, Shumin

AU - Zhang, Chengbiao

AU - Zhai, Yuanyuan

AU - Wang, Mingxiao

AU - Wu, Peng

AU - Liu, Liping

AU - Gu, Feng

AU - Zhang, Jiye

AU - Wang, Wen Hui

N1 - Funding Information: This work was supported by National Nature Science Foundation of China no. 30570673 (R-MG), no. 30770800 (R-MG), the Research Fund of High Education for Doctoral Program no. 20040226 (R-MG), Youth Science Foundation of Medical Basic Subjects of Harbin Medical University, no. 060035 (LY) and NIH HL34300 (W-HW).

PY - 2009/10

Y1 - 2009/10

N2 - 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 mol 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)- 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- 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- 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- hydroxylation-dependent metabolite 20-HETE.

AB - 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 mol 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)- 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- 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- 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- hydroxylation-dependent metabolite 20-HETE.

KW - 20-HETE

KW - CYP-o-hydroxylation

KW - Cl transport

KW - Cyclooxygenase

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U2 - 10.1038/ki.2009.287

DO - 10.1038/ki.2009.287

M3 - Article

C2 - 19641481

AN - SCOPUS:70349658732

SN - 0085-2538

VL - 76

SP - 849

EP - 856

JO - Kidney International

JF - Kidney International

IS - 8

ER -

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

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Keywords

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