Osmotic Regulation of Na + Transport Across A6 Epithelium: Interactions with Prostaglandin E 2 and Cyclic AMP

Matsumoto, Paul S.; Mo, Lijun; Wills, N. K.

doi:10.1007/s002329900292

Cited by 21 publications

(15 citation statements)

References 25 publications

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“…Previous studies have shown that amiloride-sensitive Na ϩ transport in A6 cells and native tissues is controlled by products of the enzyme PLA 2 (12)(13)(14)(15). Our results in Xenopus oocytes expressing ␣␤␥ mENaC confirm and extend these observations.…”

Section: Discussionsupporting

confidence: 90%

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Arachidonic Acid Regulates Surface Expression of Epithelial Sodium Channels

Carattino¹,

Hill²,

Kleyman

2003

Journal of Biological Chemistry

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Epithelial Na ؉ channels (ENaCs) are regulated by the phospholipase A 2 (PLA 2 ) product arachidonic acid. Pharmacological inhibition of PLA 2 with aristolochic acid induced a significant increase in amiloride-sensitive currents in Xenopus oocytes expressing ENaC. Arachidonic acid or 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolized analog of arachidonic acid, induced a time-dependent inhibition of Na ؉ transport. These effects were also observed by co-expression of a calcium-independent or a calcium-dependent PLA 2 . Channels with a truncated ␣, ␤, or ␥ C terminus were not inhibited by arachidonic acid or ETYA.

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Section: Discussionsupporting

confidence: 90%

“…In contrast, the addi-tion of blockers of PLA 2 or cyclooxygenase to the basolateral bath inhibited transepithelial Na ϩ transport. This decrease in Na ϩ transport was reversed by prostaglandin E 2 (14,15).…”

mentioning

confidence: 95%

Arachidonic Acid Regulates Surface Expression of Epithelial Sodium Channels

Carattino¹,

Hill²,

Kleyman

2003

Journal of Biological Chemistry

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“…Moreover, it was shown that infusion of prostaglandins in renal tubular fluid can increase Na ϩ reabsorption (3). Addition of exogenous PGE 2 to isosmotic solutions led to large increases in the amiloride-sensitive I sc and transepithelial conductance in A6 cells (25). PGE 2 also stimulates sodium reabsorption in MDCK-C7 cells (52).…”

Section: Discussionmentioning

confidence: 99%

“…As demonstrated in Fig. 1, mpkCCD thermore, PGE 2 under certain circumstances enhances ENaC activity in A6 (19,25) and Madin-Darby canine kidney (MDCK) cells (52). Thus we examined whether inhibition of cyclooxygenase (COX) with COX-selective nonsteroid antiinflammatory agents such as diclofenac and ibuprofen would alter ENaC-mediated sodium transport in mpkCCD c14 cells.…”

Section: Identification Of Cyp Metabolites Of Aa In Mpkccd C14 Cellsmentioning

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

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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...

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“…In A6 cell monolayers, hypotonic stress induces Na ϩ transport immediately (within 10 min) after application of the stress (18,24,26,27,29,37). Several studies revealed that hypotonic stress has a genomic and a nongenomic impact on Na ϩ reabsorption (26,29,33,37).…”

mentioning

confidence: 99%

Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells

Taruno

Niisato²,

Marunaka³

2008

American Journal of Physiology-Renal Physiology

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Taruno A, Niisato N, Marunaka Y. Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells. Am J Physiol Renal Physiol 294: F177-F186, 2008. First published October 24, 2007 doi:10.1152/ajprenal.00250.2007.-In A6 cells, a renal cell line derived from Xenopus laevis, hypotonic stress stimulates the amiloridesensitive Na ϩ transport. Hypotonic action on Na ϩ transport consists of two phases, a nongenomic early phase and a genomic delayed phase. Although it has been reported that, during the genomic phase, hypotonic stress stimulates transcription of Na ϩ transport-related genes, such as serum-and glucocorticoid-inducible kinase 1 (SGK1) and subunits of the epithelial Na ϩ channel (ENaC), increasing Na ϩ transport, the mechanism remains unknown. We focused the present study on the role of intracellular Ca 2ϩ in hypotonicity-induced SGK1 and ENaC subunit transcription. Since hypotonic stress raises intracellular Ca 2ϩ concentration in A6 cells, we hypothesized that Ca 2ϩ -dependent signals participate in the genomic action. Using real-time quantitative RT-PCR and Western blot techniques and measuring short-circuit currents, we observed that 1) BAPTA-AM and W7 blunted the hypotonicity-induced expression of SGK1 mRNA and protein, 2) ionomycin dose dependently stimulated expression of SGK1 mRNA and protein under an isotonic condition and the time course of the stimulatory effect of ionomycin on SGK1 mRNA was remarkably similar to that of hypotonic action on SGK1 mRNA, 3) hypotonic stress stimulated transcription of three ENaC subunits in an intracellular Ca 2ϩ -dependent manner, and 4) BAPTA-AM retarded the delayed phase of hypotonic stress-induced Na ϩ transport but had no effect on the early phase. These observations indicate for the first time that intracellular Ca 2ϩ plays a role as the second messenger in hypotonic stress-induced Na ϩ transport by stimulating transcription of SGK1 and ENaC subunits. sodium transport; calmodulin; W7

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Osmotic Regulation of Na + Transport Across A6 Epithelium: Interactions with Prostaglandin E 2 and Cyclic AMP

Cited by 21 publications

References 25 publications

Arachidonic Acid Regulates Surface Expression of Epithelial Sodium Channels

Arachidonic Acid Regulates Surface Expression of Epithelial Sodium Channels

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

Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells

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