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

We investigated endogenous Na-K-ATPase inhibitors, i.e. ouabain-like factors(OLFs), in the urine of salt-loaded healthy subjects. During an intake of > 30g NaCl/day 24h-urines were collected, lyophilized, redissolved and acidified to pH 3.5. With gelchromatography the inhibitory activity eluted in a post-salt fraction FIV from Sephadex G-25. When this fraction was again passed through Sephadex G-10, one of three OLFs eluted in the early subfractions FIV/1-2 close to H-ouabain and cross-reacted strongly with a ouabain antibody (NEN). Two additional OLFs with Mr around 400 eluted in a late subfraction FIV/8 which resolved after reverse-phase HPLC into a more polar OLF- (water phase) and a more apolar OLF-2 (20% acetonitrile). Only the more apolar OLF-2 cross-reacted with digoxin and ouabain antibodies. OLF-1 and OLF-2 purified to single compounds by preparative thin layer chromatography inhibited Na-K-ATPase with IC50 of around 1.5 x 10(-5) M and 1.5 x 10(-4) M, respectively. Identification of OLF-2 was first attempted because most material was available for further processing. Data from mass-spectroscopy, nuclear magnetic resonance (1H-NMR) and infrared spectroscopy characterized OLF-2 as structurally unrelated to ouabain but resembling ascorbic acid derivatives, i.e. vanadium (V) diascorbates (Mr 403) with similar elution times from RP-HPLC as OLF-2. They inhibited the enzyme in its E2-configuration with IC50 of 9 x 10(-5) M and 2 x 10(-6) M for V(IV)- and V(V)-diascorbate, respectively. OLF-1, OLF-2 and V-diascorbate raise intracellular free calcium in inner medullary collecting duct and vascular smooth muscle cells which also contract in vitro. V-diascorbate was also natriuretic in a bioassay. We suggest that V-diascorbates represent one of several OLFs excreted in human urine.
 ...
PMID:Ouabain-like factors in human urine: identification of a Na-K-ATPase inhibitor as vanadium-diascorbate adduct. 968 12

Nitric oxide (NO) derived from neuronal NO synthase (nNOS) in the kidney inner medulla has been implicated in the regulation of arterial blood pressure. The purpose of the present study was to determine the effect of high dietary NaCl on the expression of nNOS in the rat inner medullary collecting duct (IMCD). After 3 days or 3 wk of high (4.0%)-NaCl diet in rats, urinary NO-2/NO-3 excretion significantly increased. In freshly microdissected IMCD, nNOS was readily detected by immunofluorescence with polyclonal antibody, an effect that was completely blocked by neutralization of antibody with immunizing antigen. In rats fed a 4.0% NaCl diet for 3 days, IMCD nNOS mRNA, detected by RT-PCR, did not change from control values (0.3% NaCl, 19.84 +/- 1.57 x 10(3), vs. 4.0% NaCl, 20.44 +/- 3.14 x 10(3) cpm; P = not significant, n = 3). By Western blotting however, nNOS protein expression significantly increased (0.3% NaCl, 0.51 +/- 0.12, vs. 4.0% NaCl, 0.92 +/- 0.14 arbitrary units; P < 0. 05, n = 5). After 3 wk of 4.0% dietary NaCl, expression of nNOS mRNA and protein in IMCD did not differ significantly from control values. In contrast to these data, renal cortical expression of nNOS mRNA and protein was significantly decreased after 4.0% NaCl diet for 3 days. High dietary NaCl had no significant effect on expression of mRNA for inducible NO synthase (iNOS) in IMCD after either 3 days or 3 wk. In summary, our data indicate that nNOS mRNA and protein are expressed in IMCD and that high dietary NaCl differentially regulates nNOS expression in IMCD and cortex. The early increase in nNOS protein in IMCD may contribute to enhanced local production of NO and thereby represent an adaptive response to salt intake.
 ...
PMID:Effect of dietary salt on neuronal nitric oxide synthase in the inner medullary collecting duct. 968 3

Mineralocorticoid hormones regulate salt transport along the distal nephron by binding to intracellular receptors and activating gene transcription. Previous experiments showed that systemic aldosterone infusions stimulate thiazide-sensitive Na and Cl transport by distal convoluted tubule (DCT) cells; this effect could have been direct or secondary to systemic hormonal effects. Aldosterone target tissues express both mineralocorticoid receptors and the metabolic enzyme 11beta-hydroxysteroid dehydrogenase type 2. Mineralocorticoid receptors have been localized to the DCT in some experiments, but not in others. Expression of 11beta-hydroxysteroid dehydrogenase type 2 by DCT cells has not been investigated. The present experiments were designed to test the hypothesis that rat DCT cells are targets of aldosterone action. Patterns of mineralocorticoid receptor, 11beta-hydroxysteroid dehydrogenase, thiazide-sensitive Na-Cl cotransporter, and Na/Ca exchanger expression along the distal tubule were examined. A polyclonal antibody was generated to localize the thiazide-sensitive Na-Cl cotransporter. Thiazide-sensitive Na-Cl cotransporter and 11beta-hydroxysteroid dehydrogenase expression were examined using both in situ hybridization and immunocytochemistry; Na/Ca exchanger and mineralocorticoid receptor expression were examined by immunocytochemistry. The results indicate that 11beta-hydroxysteroid dehydrogenase is expressed by DCT cells, as well as connecting tubule cells and principal cells of the collecting duct; expression levels are low near the junction with the thick ascending limb and rise near the transition to the connecting tubule. Mineralocorticoid receptors are expressed by DCT cells, as well as along the thick ascending limb, connecting tubule, and collecting duct. The results indicate that components of the mineralocorticoid receptor system are expressed by DCT cells, suggesting that these cells are targets of aldosterone action.
 ...
PMID:11Beta-hydroxysteroid dehydrogenase, mineralocorticoid receptor, and thiazide-sensitive Na-Cl cotransporter expression by distal tubules. 969 56

Prostaglandin E2 is the major cyclooxygenase product of arachidonic acid metabolism produced along the nephron. This autacoid interacts with four distinct, G-protein-coupled E-prostanoid receptors designated EP1-EP4. The intrarenal distribution of each receptor has been mapped and the consequences of receptor activation examined. EP3 receptor mRNA is expressed highly in the medullary thick ascending limb (mTAL) and collecting duct (CD). EP3 receptor activation inhibits cAMP generation via Gi, thus inhibiting vasopressin-stimulated water reabsorption in the CD. EP3 receptor activation also may contribute to PGE2-mediated inhibition of NaCl absorption in the mTAL. The EP1 receptor is coupled to increased cell [Ca2+]. EP1 mRNA expression is restricted to the CD, and receptor activation inhibits Na+ absorption. PGE2 also increases cAMP generation in the cortical thick ascending limb and CD; this may be due to EP4 receptor activation. EP4 mRNA is readily detected in the CD with little detectable EP2 expression. The EP4 receptor appears to be expressed both on luminal and basolateral membranes. EP4 receptor activation also may contribute to the regulation of renin release by the juxtaglomerular apparatus. The consequences of renal EP-receptor activation for salt and water balance may be determined by the relative renal expression of each of these receptors.
 ...
PMID:Regulation of renal function by prostaglandin E receptors. 973 61

A model is presented visualizing the events leading to calcium-salt, crystal- and stone-formation inside the nephron. For each nephron segment, handling of urine components relevant to stone formation is considered and urine composition determined. This information was applied to nucleation experiments simulating passage of urine through a nephron. The model and in vitro experiments suggest that within normal transit times for the respective nephron segments, particles of a hydroxyapatite-like material first form near the bend in the Loop of Henle of juxtamedullary nephrons. From there on, calcium oxalate particles start to appear: first dihydrate, then monohydrate. In the collecting duct system, particle size increases primarily due to crystal agglomeration. Several conclusions with clinical and experimental relevance can be drawn. An increase in urinary volume does not decrease the chance of crystal formation in the Loop of Henle, but does decrease passage time through the collecting ducts, and thus, the time allowed for large particle formation. A calcium load does not increase the risk for nucleation up to the distal tubule, but does increase the risk of large particle formation in the collecting ducts. An oxalate load increases the chance for nucleation throughout the nephron. For experiments simulating crystallization processes occurring inside the nephron, diluted urines should be used. They should be diluted 16 to 50 times for testing nucleation, 2 to 30 times for testing crystal growth, and 2 to 20 times for testing crystal agglomeration. Undiluted urines may be used to mimic conditions in the pelvis and the bladder.
 ...
PMID:Crystallization and stone formation inside the nephron. 981 25

The rabbit cortical collecting duct (CCD) exhibits the capacity for active chloride absorption when basolateral Na-K-ATPase is inhibited by ouabain. The present studies examine the contribution of H,K-ATPase to this ouabain-insensitive Cl absorption and to related ion fluxes. Rabbits were fed a KCl-rich diet with no measurable Na for 4 to 13 d before isolation of the CCD for microperfusion. Application of peritubular ouabain (0.1 mM) significantly increased (P < 0.001) net luminal absorptive chloride flux (J(N)Cl) without an effect on lumen-to-bath isotopic 36Cl flux (J(lb)Cl). The H,K-ATPase inhibitor Sch 28080 (1 to 10 microM) abolished ouabain-insensitive J(N)Cl, but transepithelial voltage (V(T)) was not significantly affected. The contribution of H,K-ATPase activity on active Cl flux (J(A)Cl) and passive Cl flux (J(P)Cl) was also assessed. Ouabain significantly increased J(A)Cl and Sch 28080 inhibited J(A)Cl, but J(P)Cl was not affected by Sch 28080. To assess the contribution of changes in net bicarbonate flux (JtCO2) to changes in J(N)Cl, JtCO2 was measured under identical conditions as for J(N)Cl. Ouabain significantly increased JtCO2, and this ouabain-insensitive bicarbonate flux was inhibited by Sch 28080 without significantly affecting V(T). To assess the possibility that the CCD may possess mechanisms for neutral salt absorption, lumen-to-bath 86Rb efflux (K(Rb)), and 22Na efflux (K(Na)) were also measured. Ouabain significantly increased K(Rb), and Sch 28080 inhibited this ouabain-insensitive K(Rb). Furthermore, Sch 28080 and A80915a (a structurally distinct H,K-ATPase inhibitor) significantly inhibited K(Na) in the presence of 1 mM luminal amiloride. These observations suggest that, in addition to potassium, sodium can be transported via the H,K-ATPase. Although the CCD contains more than one cell population, the data could be fitted very well to the function of the B-type intercalated cell. A cell model is proposed for the hypothesis that ouabain-insensitive chloride absorption is mediated by the parallel operation of an apical H,K-ATPase with an apical Cl-HCO3 exchanger and that the H,K-ATPase can function, under certain conditions, as a mechanism of Na absorption.
 ...
PMID:Chloride transport by the rabbit cortical collecting duct: dependence on H,K-ATPase. 984 73

cAMP mediates many of the effects of vasopressin, prostaglandin E2, and beta-adrenergic agents upon salt and water transport in the renal collecting duct. The present studies examined the role of cAMP-dependent protein kinase (PKA) in mediating these effects. PKA is a heterotetramer comprised of two regulatory (R) subunits and two catalytic (C) subunits. The four PKA isoforms may be distinguished by their R subunits that have been designated RIalpha, RIbeta, RIIalpha, and RIIbeta. Three regulatory subunits, RIalpha, RIIalpha, and RIIbeta, were detected by immunoblot and ribonuclease protection in both primary cultures and fresh isolates of rabbit cortical collecting ducts (CCDs). Monolayers of cultured CCDs grown on semipermeable supports were mounted in an Ussing chamber, and combinations of cAMP analogs that selectively activate PKA type I vs. PKA type II were tested for their effect on electrogenic ion transport. Short-circuit current (Isc) was significantly increased by the PKA type II-selective analog pairs N6-monobutyryl-cAMP plus 8-(4-chlorophenylthio)-cAMP or N6-monobutyryl-cAMP plus 8-chloro-cAMP. In contrast the PKA type I-selective cAMP analog pair [N6-monobutyryl-cAMP plus 8-(6-aminohexyl)-amino-cAMP] had no effect on Isc. These results suggest PKA type II is the major isozyme regulating electrogenic ion transport in the rabbit collecting duct.
 ...
PMID:Type II cAMP-dependent protein kinase regulates electrogenic ion transport in rabbit collecting duct. 1019 23

This article summarizes briefly some factors responsible for edema in chronic congestive heart failure. It is now generally thought that so-called 'backward failure' is a manifestation of diastolic dysfunction, while systolic 'pump failure' is a disease that depends on two key factors: an inadequate cardiac output, and renal salt and water retention. The key elements involved in what might be termed the 'integrated volume response' are hemodynamic and renal factors. The hemodynamic factors include vasoconstriction, tachycardia and a reduced venous capacitance. These responses occur within minutes, while salt and water retention occurs over days to weeks. The key renal elements modulating sodium retention in congestive heart failure include, at a minimum, four variables. First, there is a reduction in renal blood flow produced by the almost simultaneous operation of alpha- and beta-catecholamines, antidiuretic hormone, the endothelins, and angiotensin II. Second, activation of the tubuloglomerular feedback system enhances intrarenal angiotensin II release, which augments proximal sodium absorption. In addition, beta-catechols also enhance proximal sodium absorption. A third key element involved in renal sodium retention is activation of apical sodium channels, ENaC, of principal cells in the cortical collecting tubule by aldosterone and by vasopressin. Finally, the inner medullary collecting duct becomes resistant to the action of atrial natriuretic peptide, thus adding a final dimension to the syndrome of sodium retention in underfilling.
 ...
PMID:Pathogenesis of renal sodium retention in congestive heart failure. 1020 52

The effect of altering the volumes of different body fluid compartments on the renal response to atrial natriuretic peptide (ANP) was studied in anesthetized rats before and during administration of the peptide at 170 ng/min. Four different groups were used. In the first (De), reduction of total body water content was induced by 48 h water deprivation. In the second (De+NaCl), an acute intravenous infusion after the same 48 h dehydration was used to restore the extracellular, but not the intracellular, fluid compartment. In the third (Eu+NaCl), euvolemic rats were infused with isotonic saline at the same rate as in group De+NaCl to expand both intravascular and interstitial components of extracellular fluid. In the fourth group (Eu+BSA) an infusion of hyperoncotic (6%) bovine serum albumin in isotonic saline was used to expand the intravascular volume while contracting the interstitial volume. Excretion of water and salt was predictably reduced in the De group compared with the others. This reduction was associated with increased tubular reabsorption, both upstream from the medullary collecting duct and in the duct itself. Administration of ANP did not significantly affect diuresis and saluresis, or tubular transport. By contrast, there were marked and similar diuretic and natriuretic responses to ANP in groups De+NaCl and Eu+NaCl, associated with transport inhibition primarily in the medullary collecting duct. Surprisingly, the rats infused with hyperoncotic solution (Eu+NaCl) also failed to show marked excretory or duct transport responses to ANP. According to the study design, the two nonresponding groups had, respectively, a decreased or a normal intracellular compartment, and a decreased or increased plasma volume. The common feature of both nonresponding groups was a decreased interstitial fluid compartment, whereas the two responding groups had normal or increased interstitial volume. We suggest, therefore, that a replete interstitial fluid compartment is essential for the renal response to ANP.
 ...
PMID:Body fluid volume status and the renal response to atrial natriuretic peptide in rats. 1032 39

The sequence in which the various therapies discussed above are instituted can be viewed as a continuum that parallels the severity of the underlying cirrhotic state (Figure 6). In the earliest stages of the disease urinary sodium excretion is plentiful and negative salt balance can be achieved by simply lowering dietary sodium intake. As the disease advances neurohumoral effectors become more activated initially resulting in more intense renal salt retention and later in a progressive decline in renal function. Eventually, the filtered load of sodium becomes completely reabsorbed by the tubule and the final urine becomes virtually devoid of salt. If some component of the filtered load reaches the collecting duct or beyond, spironolactone will be effective in increasing urinary sodium excretion. Once sodium reabsorption is complete, proximal to the collecting duct, then thiazides and later loop diuretics will have to be added to spironolactone to increase urinary sodium excretion. Eventually, the filtered load is completely reabsorbed proximal to the thick ascending limb of Henle. At this point the patient is resistant to the effects of diuretics and requires more invasive procedures such as repetitive large volume paracentesis to remain in salt balance. In the terminal stages of the disease the glomerular filtration rate falls to such a degree that oliguria, azotemia, and eventually uremia are present and the patient is clinically diagnosed with hepatorenal syndrome. Vasoconstrictive input focused on the kidney is severe and irreversible. Renal failure is functional in nature; however, restoration of near normal renal function can be obtained following a liver transplant.
 ...
PMID:Pathogenesis of ascites and renal salt retention in cirrhosis. 1036 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>