Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasopressin is known to acutely stimulate sodium transport in the renal collecting duct. We investigated the long-term regulation by vasopressin of the epithelial sodium channel (ENaC) in the rat kidney. Five-day infusion of dDAVP (a V(2) receptor agonist) to Brattleboro rats lacking vasopressin induced a marked increase in beta- and gamma-subunit ENaC mRNA levels in the renal cortex (beta, 85%; gamma, 100%), with no change in alpha-ENaC mRNA. Expression of beta- and gamma-ENaC mRNAs was also enhanced in lung (beta, 49%; gamma, 33%) but not in distal colon (an organ devoid of V(2) receptors). Similar results were obtained in Sprague Dawley rats after either partial water restriction or dDAVP infusion for 5 days. Transepithelial voltage and transepithelial sodium and water net fluxes were measured in isolated perfused cortical collecting ducts of Brattleboro rats. Acute addition of 2x10(-10) mol/L dDAVP to the bath increased sodium and water fluxes in the same proportion, and to a far greater extent in dDAVP-infused than in control Brattleboro rats (change in Na(+) net flux, 337+/-30 versus 49+/-11 pmol. min(-1). mm(-1), respectively; P<0.001). These effects were abolished by amiloride. Extrarenal water losses, partly originating from the lung, were reduced by high plasma vasopressin level. This study shows that vasopressin increases sodium transport in the renal collecting duct and probably in the lung, through a differential transcriptional regulation of ENaC subunits. This effect is followed by isoosmotic water reabsorption and likely contributes to the process of water conservation. It could lead to less efficient sodium excretion, however, and thus participate in some forms of salt-sensitive hypertension.
Hypertension 2001 Nov
PMID:Chronic exposure to vasopressin upregulates ENaC and sodium transport in the rat renal collecting duct and lung. 1171 12

Accumulating evidence favors the notion that perfusion of the medulla of the kidney is regulated through the effects of nitric oxide. Reduction of nitric oxide production in the medulla by local tissue infusion of nitric oxide synthase blockers leads to reduction of medullary blood flow, salt retention and hypertension. Conversely, infusion of L-arginine to increase nitric oxide abrogates hypertension and enhances medullary blood flow in animal models. Nitric oxide levels can also be controlled through its consumption by reactive oxygen species. Thus, medullary oxidative stress might influence blood pressure and sodium balance through changes in nitric oxide. Nitric oxide inhibits sodium chloride reabsorption by the thick ascending limb and collecting duct. The likelihood that some forms of hypertension result directly from pathological alteration of transporters, channels, regulatory elements or enzymes that affect medullary nitric oxide seems high.
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PMID:Role of nitric oxide in regulation of the renal medulla in normal and hypertensive kidneys. 1175 93

Phagocytes generate superoxide anion (O(2)(-)) by a classic, 5-component NADPH oxidase. O(2)(-) contributes to hypertension in spontaneously hypertensive rats (SHR). Therefore, we tested the hypothesis that NADPH oxidase expression is enhanced in the SHR kidney. We also analyzed the localization of NADPH oxidase components in SHR kidney. Renal NADPH oxidase was quantified by reverse transcription-polymerase chain reaction and Western blotting and was localized in SHR and Wistar Kyoto rat (WKY) kidney by immunohistochemistry. The mRNA for 5 subunits of phagocyte NADPH oxidase, and also for MOX1 and RENOX (NOX4), was detected in adult rat kidney. Kidneys of adult (10 weeks old) SHR had a significantly (P<0.01) greater mRNA for p47phox (SHR 0.81 +/- 0.05 versus WKY 0.37 +/- 0.01, arbitrary unit), which was confirmed by Western blotting (SHR 0.58 +/- 0.04 versus WKY 0.42 +/- 0.04, arbitrary unit; P<0.05) and by immunohistochemistry. This higher p47phox protein expression was also detected in young prehypertensive SHR (SHR 0.61 +/- 0.05 versus WKY 0.39 +/- 0.04, arbitrary unit; P<0.01). The 10-week-old SHR contained more modest but significantly (P<0.05) greater protein for p67phox (SHR 0.54 +/- 0.02 versus WKY 0.46 +/- 0.02). Immunostaining localized p47phox, p67phox, and p22phox in vasculature, macula densa, distal convoluted tubule, cortical collecting duct, and outer and inner medullary collecting ducts. The kidney of SHR expresses genes for all the main components of phagocyte NADPH oxidase, RENOX, and MOX1. There is a prominent increase in the SHR kidney of the mRNA, and protein expression of p47phox in the vasculature, macula densa, and distal nephron, which precedes development of hypertension.
Hypertension 2002 Feb
PMID:Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. 1184 96

Previous studies have indicated that NO synthesis in isolated inner medullary collecting duct cells is reduced by cationic amino acids that compete with L-arginine for cellular uptake. In the present study, we investigated the effects of chronic renal medullary infusion of cationic amino acids on renal NO concentration and mean arterial pressure (MAP) in Sprague-Dawley rats. Renal medullary infusion of L-ornithine (50 microg/kg per min) or L-lysine (50 microg/kg per min) markedly decreased NO in the medulla (vehicle, 124 +/- 11 nmol/L; L-ornithine, 45 +/- 4 nmol/L; L-lysine, 42 +/- 6 nmol/L) and increased MAP (vehicle, 111 +/- 7 mm Hg; L-ornithine, 143 +/- 6 mm Hg; L-lysine, 148 +/- 3 mm Hg) after 5 days of infusion. In contrast, intravenous infusion of the same dose of L-ornithine or L-lysine for 5 days increased plasma concentration to levels similar to those observed with intramedullary infusion but did not change NO in the medulla or alter MAP. Furthermore, the NO-suppressing and hypertensive effects of medullary interstitial infusion of L-ornithine (50 microg/kg per min) were attenuated by simultaneous infusion of L-arginine (500 microg/kg per min; NO, 97 +/- 10 nmol/L; MAP, 124 +/- 3 mm Hg). A 5-day infusion of an antisense oligonucleotide against CAT-1 (18-mer, 8.3 nmol/h) significantly decreased CAT-1 protein in the medulla, decreased NO in the medulla (scrambled oligo, 124 +/- 10 nmol/L; antisense oligo, 67 +/- 11 nmol/L), and increased MAP (scrambled oligo, 113 +/- 2 mm Hg; antisense oligo, 130 +/- 2 mm Hg). These results suggest that uptake of L-arginine by cationic amino acid transport systems in the renal medulla plays an important role in the regulation of medullary NO and MAP in rats.
Hypertension 2002 Feb
PMID:Cationic amino acid transport in the renal medulla and blood pressure regulation. 1184 99

The present study was designed to determine whether arginine vasopressin (AVP) stimulates NO production in the epithelial collecting duct cells of the inner medulla (IMCDs) and if this is mediated through Ca(2+) signaling. Thin tissue layers containing IMCDs were dissected from Sprague-Dawley rats. Intracellular Ca(2+) concentration ([Ca(2+)](i)) and NO production were measured in IMCDs by a fluorescence imaging system with the use of fura 2-AM and the cell-permeable form of the NO-sensitive dye 4,5-diaminofluorescein (DAF-2), respectively. AVP (100 nmol/L) produced a rapid peak increase in [Ca(2+)](i) of 320 +/- 70 nmol/L within a few seconds and a sustained increase of 120 +/- 62 nmol/L. The peak increase in [Ca(2+)](i) was followed by a significant increase of NO production (34 +/- 7 U). This was similar to that produced by 20 micromol/L of the NO donor DETA-NONOate (42 +/- 11 U). The NO scavenger carboxy-PTIO (100 micromol/L) or depletion of [Ca(2+)](i) by preincubation with 5 micromol/L of the Ca(2+)-ATPase inhibitor thapsigargin in Ca(2+)-free buffer abolished the NO response to AVP. We conclude that AVP mobilizes Ca(2+) to produce NO in IMCDs.
Hypertension 2002 Feb
PMID:Vasopressin increases intracellular NO concentration via Ca(2+) signaling in inner medullary collecting duct. 1188 91

The Na/K pump of vascular smooth muscle cells (VSMC) and renal epithelial cells (REC) is viewed as a target of digitalis and endogenous ouabain (EO), leading to the development of hypertension. In this study, we compared the effect of ouabain on Na/K pump activity and the intracellular content of monovalent cations in VSMC and REC obtained from rats, humans and dogs. In VSMC from the rat aorta, ouabain inhibited maximal Na/K pump activity measured as the rate of 86Rb influx in Na+-loaded cells, with an ID50 of approximately 20-30 microM without any differences between two strains of normotensive rats (WKY and BN.1x) and three substrains of spontaneously hypertensive rats (SHR). Half-maximal inhibition of the Na/K pump in REC from the rat inner medullary collecting duct was observed at approximately 20 microM of ouabain. In contrast to rat cells, half-maximal inhibition of 86Rb influx in VSMC from human coronary arteries and in REC from the Madin-Darby canine kidney was seen at approximately 0.03 and 0.1 microM ouabain, respectively. At concentrations lower than 100 microM, ouabain did not affect the intracellular content of exchangeable Na+ and K+ in rat VSMC, measured as the steady-state distribution of 22Na and 86Rb, whereas in human VSMC, it increased the intracellular Na+/K+ ratio with an ID50 of approximately 0.5 microM. Keeping in mind that the circulating level of administered digitalis and EO does not exceed 10(-9) M, our results strongly suggest that the involvement of these compounds in the pathogenesis of hypertension in rats is not mediated by inhibition of the alpha1-isoform of the Na/K pump in VSMC and REC. Alternative mechanisms of the involvement of EO and ouabain-like factors in the development of hypertension are considered.
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PMID:The alpha1-Na/K pump does not mediate the involvement of ouabain in the development of hypertension in rats. 1192 53

The epithelial Na+ channel (ENaC) forms the pathway for Na+ absorption in the kidney collecting duct and other epithelia. Dominant gain-of-function mutations cause Liddle's syndrome, an inherited form of hypertension resulting from excessive renal Na+ absorption. Conversely, loss-of-function mutations cause pseudohypoaldosteronism type I, a disorder of salt wasting and hypotension. Thus, ENaC has a critical role in the maintenance of Na+ homeostasis and blood pressure control. Altered Na+ absorption in the lung may also contribute to the pathogenesis of cystic fibrosis. Epithelial Na+ absorption is regulated in large part by mechanisms that control the expression of ENaC at the cell surface. Nedd4, a ubiquitin protein ligase, binds to ENaC and targets the channel for endocytosis and degradation. Liddle's syndrome mutations disrupt the interaction between ENaC and Nedd4, resulting in an increase in the number of ENaC channels at the cell surface. Aldosterone and vasopressin also regulate Na+ absorption to defend against hypotension and hypovolemia. Both hormones increase the expression of ENaC at the cell surface. The goal of this review is to summarize recent data on the regulation of ENaC expression at the cell surface.
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PMID:The epithelial Na+ channel: cell surface insertion and retrieval in Na+ homeostasis and hypertension. 1194 47

An apical serine protease, channel-activating protease 1 (CAP1), augments sodium transport in A6 cells. Prostasin, a novel serine protease originally purified from seminal fluid, has been proposed to be the mammalian ortholog of CAP1. We have recently found functional evidence for a similar protease activity in the M-1 cortical collecting duct cell line. The purposes of the present studies were to determine whether prostasin (or CAP1) is present in collecting duct cells by use of mouse M-1 cells, to sequence mouse prostasin, and to further characterize the identity of the serine protease activity and additional functional features in M-1 cells. Using mouse expressed sequence tag sequences that are highly homologous to the published human prostasin sequence as templates, reverse transcription-polymerase chain reaction and RACE (rapid amplification of cDNA ends) were used to sequence mouse prostasin mRNA, which shows 99% identical to published mouse CAP1 sequence. A single 1800-bp transcript was found by Northern analysis, and this was not altered by aldosterone. Equivalent short-circuit current (I(eq)), which represents sodium transport in these cells, dropped to 59+/-3% of control value within 1 hour of incubation with aprotinin, a serine protease inhibitor. Trypsin increased the I(eq) in aprotinin-treated cells to the value of the control group within 5 minutes. Application of aprotinin not only inhibited amiloride sensitive I(eq) but also reduced transepithelial resistance (R(te)) to 43+/-2%, an effect not expected with simple inhibition of sodium channels. Trypsin partially reversed the effect of aprotinin on R(te). Another serine protease inhibitor, soybean trypsin inhibitor (STI), decreased I(eq) in M-1 cells. STI inhibited I(eq) gradually over 6 hours, and the inhibition of I(eq) by 2 inhibitors was additive. STI decreased transepithelial resistance much less than did aprotinin. Neither aldosterone nor dexamethasone significantly augmented protease activity or prostasin mRNA levels, and in fact, dexamethasone decreased prostasin mRNA expression. In conclusion, although prostasin is present in M-1 cells and probably augments sodium transport in these cells, serine proteases probably have other effects (eg, resistance) in the collecting duct in addition to effects on sodium channels. Steroids do not alter these effects in M-1 cells. Additional proteases are likely also present in mouse collecting duct cells.
Hypertension 2002 Apr
PMID:Serine protease activity in m-1 cortical collecting duct cells. 1196 40

This study focuses on certain aspects of the renal structure of the giraffe, with some implications as to its function. About 4,000 collecting ducts open at the truncated end of a curved crest that juts into the renal pelvis as the inner medulla (IM). Extensions of the pelvis pass between the medullary (MP) and vascular (VP) processes almost to the corticomedullary border. The MPs contain an IM and an outer medulla (OM) containing clusters of capillaries (vascular bundles). The VPs contain the interlobar arteries and veins. All of the IM and almost all of the OM, with its vascular bundles, are bathed with pelvic urine. The cortex comprises 63% of the parenchyma. The OM has nine times the mass of the IM. The IM comprises 4% of the parenchyma. The ratio of mass of the adult cortex to the medulla is 1.7:1.0, and the number of glomeruli per kidney is 6.6 x 10(6). Glomerular mass is 6.2-6.7% of renal mass in the adult and 5.2% in the 6-month-old calf. The dimensions of the glomerular capsules are the same across the thickness of the cortex. Every terminal collecting duct drains an estimated 1,650 nephrons. In the adult giraffe the ratio of thickness of the muscularis of the main renal artery (RA) to its diameter is 0.117 (right RA) and 0.132 (left RA). These ratios are close to those in rhinoceros and ox but greater than in man. The visceral arteries (celiac, anterior mesenteric, and renal) have about the same muscularis : diameter ratio. Giraffes have arterial hypertension, but atherosclerosis is apparently absent and serum lipid fractions are low.
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PMID:Kidney of giraffes. 1199 78

The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in fluid and electrolyte homeostasis and consists of alpha, beta, and gamma subunits. The carboxyl terminus of each ENaC subunit contains a PPXY motif that is believed to be important for interaction with the WW domains of the ubiquitin-protein ligases, Nedd4 and Nedd4-2. Disruption of this interaction, as in Liddle's syndrome where mutations delete or alter the PPXY motif of either the beta or gamma subunits, has been shown to result in increased ENaC activity and arterial hypertension. Here we present evidence that N4WBP5A, a novel Nedd4/Nedd4-2-binding protein, is a potential regulator of ENaC. In Xenopus laevis oocytes N4WBP5A increases surface expression of ENaC by reducing the rate of ENaC retrieval. We further demonstrate that N4WBP5A prevents sodium feedback inhibition of ENaC possibly by interfering with the xNedd4-2-mediated regulation of ENaC. As N4WBP5A binds Nedd4/Nedd4-2 via PPXY motif/WW domain interactions and appears to be associated with specific intracellular vesicles, we propose that N4WBP5A functions by regulating Nedd4/Nedd4-2 availability and trafficking. Because N4WBP5A is highly expressed in native renal collecting duct and other tissues that express ENaC, it is a likely candidate to modulate ENaC function in vivo.
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PMID:Regulation of the epithelial sodium channel by N4WBP5A, a novel Nedd4/Nedd4-2-interacting protein. 1205 Jan 53


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