Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL

Gu, Ruimin; Wei, Yuan; Jiang, Houli; Balazy, Michael; Wang, Wenhui

doi:10.1152/ajprenal.2001.280.2.f223

Cited by 25 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because the Ca 2ϩ -sensing receptor is located in the basolateral membrane of the mTAL, it is conceivable that the stimulation of the Ca 2ϩ -sensing receptor may also inhibit the basolateral 50-pS K channel. Moreover, we have previously demonstrated that 20-HETE production increased in the mTAL obtained from rats on a K-deficient diet (12). Therefore, it is possible that basolateral K channel activity differs between mTALs from animals on a normal-K diet and from those on a low-K diet.…”

Section: Discussionmentioning

confidence: 95%

Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Wang

2002

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

We have used the patch-clamp technique to study the effect of arachidonic acid (AA) on the basolateral K channels in the medullary thick ascending limb (mTAL) of rat kidney. An inwardly rectifying 50-pS K channel was identified in cell-attached and inside-out patches in the basolateral membrane of the mTAL. The channel open probability (Po) was 0.51 at the spontaneous cell membrane potential and decreased to 0.25 by 30 mV hyperpolarization. The addition of 5 M AA decreased channel activity, identified as NPo, from 0.58 to 0.08 in cell-attached patches. The effect of AA on the 50-pS K channel was specific because 10 M cis-11,14,17-eicosatrienoic acid had no significant effect on channel activity. To determine whether the effect of AA was mediated by AA per se or by its metabolites, we examined the effect of AA on channel activity in the presence of indomethacin, an inhibitor of cyclooxygenase, or N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS), an inhibitor of cytochrome P-450 monooxygenase. Inhibition of cyclooxygenase increased channel activity from 0.54 to 0.9. However, indomethacin did not abolish the inhibitory effect of AA on the 50-pS K channel. In contrast, inhibition of cytochrome P-450 metabolism not only increased channel activity from 0.49 to 0.83 but also completely abolished the effect of AA. Moreover, addition of DDMS can reverse the inhibitory effect of AA on channel activity. The notion that the effect of AA was mediated by cytochrome P-450-dependent metabolites of AA is also supported by the observation that addition of 100 nM of 20-hydroxyeicosatetraenoic acid, a main metabolite of AA in the mTAL, can mimic the effect of AA. We conclude that AA inhibits the 50-pS K channel in the basolateral membrane of the mTAL and that the effect of AA is mainly mediated by cytochrome P-450-dependent metabolites of AA.cyclooxygenase; cytochrome P-450 -oxidation; 20-hydroxyeicosatetraenoic acid; basolateral K channel K CHANNELS IN THE BASOLATERAL membrane of the medullary thick ascending limb (mTAL) play an important role in the regulation of epithelial transport in the loop of Henle. The basolateral K channels in the mTAL are responsible for K recycling across the basolateral membrane and participate in generating the cell membrane potential (Fig.

show abstract

Section: Discussionmentioning

confidence: 95%

Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Wang

2002

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…However, these results are confounded because heme oxygenase inducers also stimulate the formation of the vasodilatory gas carbon monoxide and may influence nitric oxide synthase activity and produce vasodilatory factors via the cGMP pathway (35). Dibromo-olefinic fatty acids are relatively specific inhibitors of arachidonic acid -/( -1)-hydroxylation and have been extensively used to characterize 20-HETE biological effects in vitro and in situ (17,21,46,54). The most potent inhibitor of arachidonic acid -hydroxylation to date is N-hydroxy-NЈ-(4-butyl-2-methylphenyl)-formamidine (HET-0016) (33).…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid ω-hydroxylase activity

Xu¹,

Straub

Pak³

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

is a potent vasoconstrictor that is implicated in the regulation of blood pressure. The identification of selective inhibitors of renal 20-HETE formation for use in vivo would facilitate studies to determine the systemic effects of this eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20-HETE formation. A single dose of 10-SUYS caused an acute reduction in mean arterial blood pressure in 8-wk-old spontaneously hypertensive rats. The decrease in mean arterial pressure was maximal 6 h after 10-SUYS treatment (17.9 Ϯ 3.2 mmHg; P Ͻ 0.05), and blood pressure returned to baseline levels within 24 h after treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20-HETE formation in vivo and attenuation of the vasoconstrictor response of renal interlobar arteries to ANG II in vitro. These results provide further evidence that 20-HETE plays an important role in the regulation of blood pressure in the spontaneously hypertensive rat.spontaneously hypertensive rat; cytochrome P-450; sodium 10-undecynyl sulfate; 20-hydroxyeicosatetraenoic acid CYTOCHROMES P-450 (CYPs) are major catalysts of renal arachidonic acid metabolism, and CYP-derived eicosanoids have been implicated in the regulation of vascular tone and renal function (9, 41). The major products of CYP-catalyzed arachidonic acid metabolism are the -hydroxylated metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) and four regio-and stereoisomeric epoxyeicosatrienoic acids (EETs). EETs are further hydrated to the corresponding dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH) (53). The major CYP eicosanoid formed in rat and human renal microsomes is 20-HETE (8, 28). 20-HETE depolarizes vascular smooth muscle cells by inhibiting Ca 2ϩ -activated K ϩ channels and increases the conductance of L-type Ca 2ϩ channels, both effects leading to Ca 2ϩ entry and potent vasoconstriction (14,56). Additional roles for 20-HETE include mediation of the myogenic response of small cerebral and renal arteries to elevations in transmural pressure, and the autoregulation of cerebral and renal blood flow, glomerular filtration rate, and tubular glomerular feedback (13,22,58). In renal tubules 20-HETE inhibits Na ϩ -K ϩ -ATPase, a Na ϩ -K ϩ -2Cl Ϫ cotransporter, and 70-pS K ϩ channels, leading to natriuresis and diuresis (3,30,38). EETs and DHETs are generally considered vasodilatory, although they exhibit both vasodilatory and vasoconstrictive properties in vitro, depending on the vascular bed and species that are studied (20,55,57). A number of studies suggest that EETs are endothelium-derived hyperpolarizing factors that mediate vasodilation by activation of Ca 2ϩ -dependent K ϩ channels in vascular smooth muscle cells (6,7,10). Both EETs and DHETs can also mediate natriuresis and diuresis by inhibition of Na ϩ -K ϩ -ATPase in rat proximal tubules (38).The effects of CYP eicosanoids in the regulation of vascular tone and renal function have pr...

show abstract

“…20-HETE and EETs have effects on thick ascending limb (TAL) cells that decrease sodium reabsorption. The inhibitory action of 20-HETE on Na ϩ transport in the TAL is associated with closure of the apical 70-pS K ϩ channels (10,50). AA also inhibits the 50-pS K ϩ channels in the basolateral membrane of the mTAL mainly through cytochrome P-450-dependent metabolites of AA (11).…”

mentioning

confidence: 99%

Effects of cytochromeP-450 metabolites of arachidonic acid on the epithelial sodium channel (ENaC)

Pavlov¹,

Ilatovskaya

Levchenko³

et al. 2011

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Previous studies have indicated that arachidonic acid (AA) and its metabolite 11,12-EET but not other regioisomers of EETs inhibit ENaC activity in the collecting duct. The goal of this study was to investigate the endogenous metabolism of AA in cultured mpkCCD c14 principal cells and the effects of these metabolites on ENaC activity. Liquid chromatography/mass spectrometry analysis of the mpkCCD c14 cells indicated that these cells produce prostaglandins, 8,9-EET, 11,12-EET, 14,15-EET, 5-HETE, 12/8-HETE, and 15-HETE, but not 20-HETE. Single-channel patch-clamp experiments revealed that 8,9-EET, 14,15-EET, and 11,12-EET all decrease ENaC activity. Neither 5-, 12-, nor 15-HETE had any effect on ENaC activity. Diclofenac and ibuprofen, inhibitors of cyclooxygenase, decreased transepithelial Na ϩ transport in the mpkCCDc14 cells. Inhibition of cytochrome P-450 (CYP450) with MS-PPOH activated ENaC-mediated sodium transport when cells were pretreated with AA and diclofenac. Coexpression of CYP2C8, but not CYP4A10, with ENaC in Chinese hamster ovary cells significantly decreased ENaC activity in whole-cell experiments, whereas 11,12-EET mimicked this effect. Thus both endogenously formed EETs and their exogenous application decrease ENaC activity. Downregulation of ENaC activity by overexpression of CYP2C8 was PKA dependent and was prevented by myristoylated PKI treatment. Biotinylation experiments and single-channel analysis revealed that long-term treatment with 11,12-EET and overexpression of CYP2C8 decreased the number of channels in the membrane. In contrast, the acute inhibitory effects are mediated by a decrease in the open probability of the ENaC. We conclude that 11,12-EET, 8,9-EET, and 14,15-EET are endogenously formed eicosanoids that modulate ENaC activity in the collecting duct. aldosterone; eicosanoids; 11,12-EET; 8,9-EET; 14,15-EET; 20-HETE; prostaglandins THE EPITHELIAL SODIUM CHANNEL (ENaC) is thought to represent the rate-limiting step for sodium absorption in the renal collecting duct. Consequently, ENaC is a central effector that impacts blood volume and systemic arterial pressure regulation. ENaC is localized to the luminal plasma membrane of epithelial cells and is involved in Na ϩ homeostasis. Multiple factors regulate the renal handling of sodium, including the renin-angiotensin-aldosterone system, nitric oxide, arachidonic acid (AA), and its metabolites. AA is primarily metabolized by cytochrome P-450 enzymes to 19-and 20-HETE and EETs (5,6-, 8,9-, 11,12-, and 14,15-EET) in the renal cortex, and these compounds have been shown to play critical roles in the regulation of renal tubular and vascular function (34). Cytochrome P-450 members of the CYP2C and CYP4A families are the predominant epoxygenases and -hydroxylase enzymes expressed in the kidney (5). The cyp4A isoform has been reported to be expressed in the cortical collecting ducts (CCD) (15). Knockdown of the Cyp4a10 gene in mice produces a salt-sensitive form of hypertension that is associated with alterations in the activity of ENaC (28...

show abstract

Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL

Cited by 25 publications

References 34 publications

Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Arachidonic acid inhibits K channels in basolateral membrane of the thick ascending limb

Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid ω-hydroxylase activity

Effects of cytochromeP-450 metabolites of arachidonic acid on the epithelial sodium channel (ENaC)

Contact Info

Product

Resources

About