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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The roles of elevated cell sodium concentrations and the angiotensin-aldosterone system (AAS) in the structural and functional adaptation of the distal tubule and collecting duct system to a chronic increase of sodium delivery were examined using electron microprobe and quantitative morphologic/stereologic analyses. Studies were performed on rats given the loop diuretic torasemide acutely (20 min) or chronically (12 days), either alone or in combination with the angiotensin-converting enzyme (ACE) inhibitor, enalapril. In the sodium-absorbing cells of the distal tubule and cortical collecting duct-that is, in distal convoluted tubule (DCT), connecting tubule (CNT) and principal cells-an acute increase in sodium delivery caused a significant rise in intracellular sodium concentration and rubidium uptake, the latter an index of in vivo Na,K(Rb)-ATPase activity. The elevated cell sodium concentrations returned to, or close to, control values during chronic torasemide treatment. Intracellular rubidium concentrations, measured after a 30-second rubidium exposure, were not different from controls in DCT and CNT cells but were still higher in principal cells. Since, however, the distribution space for rubidium was significantly increased in chronic torasemide animals, rubidium uptake, and hence Na,K-ATPase activity, must have increased in proportion to cell volume in DCT and CNT cells, but more than proportionately in principal cells. When ACE was inhibited during chronic torasemide, the epithelial volume of DCT and cortical collecting duct (CCD) was increased mainly by lengthening and not, as was the case in rats given torasemide alone, by thickening of the tubule wall. Adaptation of the proximal tubule exclusively by lengthening was not affected by inhibition of the ACE. These data indicate that changes in cell ion composition may participate in initiating cell processes leading to adaptation of distal nephron segments to chronically increased salt delivery. Inhibition of the ACE reverses the torasemide-induced increase in apparent Na pump density in principal cells and seems to shift the relationship between hypertrophy and hyperplasia noted in DCT and CCD after chronic torasemide in favor of hyperplasia.
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PMID:Inhibition of angiotensin-converting enzyme modulates structural and functional adaptation to loop diuretic-induced diuresis. 899 15

The present experiments were designed to examine the function of Na/K pumps from Dahl salt-sensitive (S) and salt-resistant (R) rats. Previous reports have suggested that there is a difference in primary sequence in the alpha 1 subunit, the major Na/K pump isoform in the kidney. This sequence difference might contribute to differences in NaCl excretion in these two strains which in turn could influence the systemic blood pressure. Using "back-door" phosphorylation of pumps isolated from basolateral membranes of kidney cortex, we found no differences between S and R strains. We also examined the Na/K pumps from cultured inner medullary collecting duct (IMCD) cells. This approach takes advantage of the fact that monolayers cultured from S rats transport about twice as much Na+ as monolayers cultured from R rats. In cells whose apical membrane was made permeable with amphotericin B, comparison of the affinities for ouabain, Na+, and K+, respectively, showed only small or no differences between S and R monolayers. Ouabain binding showed no difference in the number of Na/K pumps on the basolateral membrane of cultured cells, despite a 2-fold difference in Na+ transport rates. The analysis of the steady-state Na+ transport indicates that Na/K pumps in IMCD monolayers from S rats operate at a higher fraction of their maximum capacity than do pumps in monolayers from R rats. The results, taken together, suggest that the major reason for the higher rate of Na+ transport in S monolayers is because of a primary increase in the conductive permeability of the apical membrane to Na+. They suggest that the epithelial Na+ channel is intrinsically different or differently regulated in S and R rats.
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PMID:The basis of higher Na+ transport by inner medullary collecting duct cells from Dahl salt-sensitive rats: implicating the apical membrane Na+ channel. 907 Apr 59

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is expressed in all nephron segments. Although mutations in CFTR are not associated with major changes in renal function, drug excretion by the kidneys is altered in cystic fibrosis (CF) as is the ability of the kidneys to concentrate and dilute the urine and excrete a salt load. It is not clear if these changes in renal function are secondary to decreased extracellular fluid volume caused by excessive losses of NaCl in sweat and feces or if they are related to primary defects in renal function caused by mutations in CFTR. Considerable evidence supports a role for CFTR in mediating Cl- secretion by the distal tubule, principal cells in the cortical collecting duct (CCD) and the inner medullary collecting duct (IMCD). In addition, CFTR is responsible for Cl- secretion into the lumen of cysts in polycystic kidneys and, therefore, contributes to cyst enlargement. Under some conditions--when Na+ absorption across the apical membrane of principal cells in the CCD is stimulated and the apical membrane potential is depolarized--the electrochemical gradient for Cl- will support Cl- absorption via CFTR Cl- channels. In addition to its function as a 3',5'-cAMP-activated Cl- channel, CFTR may play a role in intracellular vesicle acidification, protein processing, protein trafficking, secretion of ATP and the regulation of the epithelial Na channel (ENaC) and the secretory K+ channel (ROMK2) which mediate Na+ and K+ transport, respectively, across the CCD. Thus, CFTR may regulate Na+ and K+ excretion by the kidneys. The most common mutation in CFTR is delta F508, a mutation which causes improper folding of CFTR such that it is retained within the endoplasmic reticulum where it is degraded. Thus, in the majority of cases, CF is a trafficking disease. However, nothing is known about the intracellular trafficking of CFTR in the kidney. In preliminary studies we have developed a living cell model to study the intracellular trafficking of CFTR and delta F508-CFTR in renal epithelial cells in real time. Our ultimate goal is to elucidate the intracellular trafficking of CFTR and to identify therapeutic approaches to restore normal function to renal cells in CF and to block CFTR-mediated Cl- secretion in cysts in polycystic kidneys.
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PMID:Cystic fibrosis transmembrane conductance regulator (CFTR) and renal function. 926 86

In this little essay I describe recent advances in understanding the problem of salt sensitivity and salt resistance involved in the control of blood volume and blood pressure. Genetic evidence links the recently characterized epithelial sodium channel (ENaC) and the potassium channel (ROMK-1) to monogenic diseases in humans, characterized by a renal salt-losing syndrome. A loss of function mutations in ROMK-1 gene causes in some pedigrees the syndrome of Bartter, characterized by metabolic alkalosis and a severe salt-losing syndrome. A loss of function mutations in ENaC genes causes pseudohypoaldosteronism-type 1, characterized by hypovolaemia, hyperkaliaemia, metabolic acidosis and hypotension. ENaC and ROMK-1 are expressed in the apical membrane of principal cells of the cortical collecting duct and their role in Na/K balance is briefly reviewed.
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PMID:Lose salt and gain a friend! A tribute to Gerhard Giebisch. 926 95

Can urolithiasis start as an intratubular event? Under severe hyperoxaluric conditions in animal models at least crystal formation can. Recently models have been presented that assess the chances of crystal formation under more normal conditions. These models describe changes in fluid composition as this passes through the nephron, these conditions being simulated in in vitro experiments. It appears that under naturally occurring intratubular conditions calcium-salt crystallization takes place within the time tubular fluid normally spends in the nephron. Precipitation starts with a calcium-phosphate phase under conditions found in the thin lambs. This crystalline phase then (partly) dissolves when collecting duct conditions are used, thereby inducing formation of calcium oxalates. Under these conditions the latter increase in size by way of crystal growth and agglomeration. Large particle formation and cell adhesion can eventually result in particle retention and subsequent stone formation. Viewing urolithiasis as originally an intratubular event has consequences for in vitro experiments and treatments, which are discussed in this paper.
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PMID:Intratubular crystallization events. 928 50

The role of C-type natriuretic peptide (CNP) and its guanylyl cyclase-linked receptors in mediating salt secretion by the rectal gland of the spiny dogfish shark (Squalus acanthias) was investigated using HS-142-1, a competitive inhibitor of the binding of natriuretic peptides to their guanylyl cyclase receptors. CNP binds to receptors and activates guanylyl cyclase in rectal gland membranes in a way that is inhibited by HS-142-1. Guanylyl cyclase activation in rectal gland membranes is far more sensitive to CNP than to atrial natriuretic peptide, whereas the reverse is true for membranes derived from mammalian (rabbit) renal collecting duct cells. HS-142-1 inhibited the stimulatory effect of CNP on ouabain-inhibitable oxygen consumption by rectal gland tubules. In explanted rectal glands continuously perfused with blood from intact donor sharks, HS-142-1 inhibited the increase in salt secretion normally provoked by infusing isotonic saline solutions into the donor animal. These results strongly support the view that CNP released into the systemic circulation in response to volume expansion mediates the secretion of chloride by the rectal gland via receptors linked to guanylyl cyclase.
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PMID:Role of guanylyl cyclase receptors for CNP in salt secretion by shark rectal gland. 936 5

NG-monomethylarginine (L-NMA) and asymmetric NG, NG-dimethylarginines (ADMA) are endogenous inhibitors of cellular L-arginine uptake and/or nitric oxide (NO) synthesis that are implicated in renal parenchymal and Dahl salt-sensitive hypertension. Since the L-arginine:(L-NMA + ADMA) ratio determines NO synthase (NOS) activity, we compared the immunohistochemical distribution of NOS with NG, NG-dimethylarginine dimethylaminohydrolase (DDAH), which inactivates dimethylarginines (DMA) and L-NMA by hydrolysis to L-citrulline. Neuronal NOS (nNOS) was expressed predominantly in tubular epithelial cells of macula densa (MD), endothelial NOS (eNOS) in vascular endothelial cells (EC), and inducible NOS (iNOS) quite widely in tubular epithelium, including proximal tubules (PT), thick ascending limbs of Henle (TAL), distal convoluted tubule and intercalated cells (IC) of the collecting duct. Immunostaining for DDAH was present in PT, TAL, MD, and IC, and was also present in the glomerulus, Bowman's capsule, and endothelium of blood vessels. DDAH was detected in small vesicles of TAL and PT by electron microscopic (EM) immunocytochemistry. To study the effects of methylarginines on tubuloglomerular feedback (TGF) response, vehicle or methylarginines (10(-3) M) were added to artificial tubular fluid (ATF) perfused orthogradely from the late PT at 40 nl. min-1 while assessing changes in glomerular capillary pressure from proximal stop flow pressure (PSF). Whereas the maximal TGF responses were unchanged by vehicle (delta TGF 0 +/- 0%) or symmetric DMA (SDMA; +1 +/- 2%, NS), they were enhanced by L-NMA (+22 +/- 4%, P < 0.001) and asymmetric DMA (ADMA; +28 +/- 3%, P < 0.001). Since L-arginine transport can regulate renal epithelial NO generation, methylarginines (10(-3) M) or vehicle were co-perfused orthogradely with [3H]-L-arginine from the late PT and collected at the early distal tubule to study arginine uptake from the perfused loop of Henle. All methylarginines reduced fractional loop [3H] absorption significantly (P < 0.001; vehicle, 84 +/- 6; ADMA, 49 +/- 6; SDMA, 56 +/- 6; L-NMA, 41 +/- 6%). In conclusion, sites of DDAH expression in the vasculature or nephron are all sites of expression of an isoform of NOS. L-NMA, ADMA, and SDMA all inhibit renal tubular L-arginine uptake, whereas L-NMA and ADMA, but not SDMA, enhance TGF responses. Therefore, DDAH may regulate the cellular L-arginine: methylarginine levels in specific renal cells, thereby governing cell-specific L-arginine uptake and NO generation in renal tubular epithelium.
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PMID:Colocalization of demethylating enzymes and NOS and functional effects of methylarginines in rat kidney. 940 5

Serum potassium is normally maintained within a narrow range through an exquisite balance between cellular K+ efflux and influx, and between the intake and output of potassium from the body. Ultimately such balances are determined by cell membrane molecules which effect K+ transfer from one milieu to another. Over the last decade, electrophysiological and molecular techniques of study, briefly reviewed in this article, have helped to define the biochemical and functional characteristics of many of the molecules responsible for potassium homeostasis. When combined with molecular genetics, the same technology allows for the ultimate definition of hereditary or familial disease states characterized by hypokalemia. Familial hypokalemic periodic paralysis is associated with mutations of the dihydropyridine receptor gene encoding the L-type Ca+2 channel, but how such mutations result in episodic hypokalemia and paralysis remains a mystery. Mutations in several genes involved in renal ion transport also result in hypokalemia. Among them, Liddle's syndrome, or pseudohyperaldosteronism, has been linked to increased surface expression of the epithelial sodium channel (ENaC) responsible for Na+ transport in the cortical collecting duct. On the other hand, Bartter's syndrome, characterized by defective salt reabsorption by the ascending limb of Henle's loop, is associated with mutations in either the NKCC2 gene encoding the loop's 1Na+-1K+-2Cl- cotransporter, or in the ROMK gene, which allows K+ recycling in the loop to occur from cell to lumen, making Na+ reabsorption via the cotransporter possible. In Gitelman's syndrome, which clinically appears as a milder form of Bartter's, the abnormal gene encodes the thiazide sensitive Na+-Cl- cotransporter operating in the distal convoluted tubule.
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PMID:Hypokalemia and the pathology of ion transport molecules. 945 87

Recently, we reported that primary cultures of inner medullary collecting duct cells from Dahl salt-sensitive (S) rats absorb more Na+ than do cells cultured from Dahl salt-resistant (R) rats. To begin to evaluate the molecular basis for this difference, we selected four candidate gene products that on the basis of their physiology and genetics could participate in regulation of Na+ transport by these cells. During 24-hour exposure, inhibitors of the cytochrome P450 enzymes had no effect on Na+ transport by either S or R monolayers. Twenty-four-hour exposure to NG-monomethyl-L-arginine (0.5 mmol/L), a nonspecific inhibitor of NO synthase, also had no effect on Na+ transport by either S or R monolayers. Neither atrial natriuretic peptide 1-28 (100 nmol/L) nor 8-Br-cyclic GMP (100 micromol/L) had any short-term effect on Na+ transport by either S or R monolayers. 18-Hydroxy-11-deoxycorticosterone (100 nmol/L), an adrenocorticoid hormone that is produced in greater amounts in S rats, stimulated Na+ transport by both S and R monolayers via the mineralocorticoid receptor; however, its effect was less potent than aldosterone. Congenic rats in which the R isoform of the 11beta-hydroxylase gene was bred onto the S background had monolayers that transported Na+ at a rate similar to the S rats. These results demonstrate that neither cytochrome P450 genes, NO synthase genes, the atrial natriuretic peptide receptor gene, nor the 11beta-hydroxylase gene is a likely candidate to explain the difference in Na+ transport between S and R inner medullary collecting duct monolayers in primary culture.
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PMID:Candidate genes in the regulation of Na+ transport by inner medullary collecting duct cells from Dahl rats. 946 Dec 29

The present studies were undertaken to determine the effect of dietary salt intake on the renal expression of cyclooxygenase-1 (COX-1) and -2 COX-2). Protein levels were assessed by Western blotting, and mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) on cDNA prepared from kidney regions, dissected nephron segments, and cultured renal cells. Both isoforms were expressed at high levels in inner medulla (IM), with low levels detected in outer medulla and cortex. COX-1 mRNA was present in the glomerulus and all along the collecting duct, whereas COX-2 mRNA was restricted to the macula densa-containing segment (MD), cortical thick ascending limb (CTAL), and, at significantly lower levels, in the inner medullary collecting duct. Both isoforms were highly expressed at high levels in cultured medullary interstitial cells and at lower levels in primary mesangial cells and collecting duct cell lines. Maintaining rats on a low- or high-NaCl diet for 1 wk did not affect expression of COX-1. In IM of rats treated with a high-salt diet, COX-2 mRNA increased 4.5-fold, and protein levels increased 9.5-fold. In contrast, cortical COX-2 mRNA levels decreased 2.9-fold in rats on a high-salt diet and increased 3.3-fold in rats on a low-salt diet. A low-salt diet increased COX-2 mRNA 7.7-fold in MD and 3.3-fold in CTAL. Divergent regulation of COX-2 in cortex and medulla by dietary salt suggests that prostaglandins in different kidney regions serve different functions, with medullary production playing a role in promoting the excretion of salt and water in volume overload, whereas cortical prostaglandins may protect glomerular circulation in volume depletion.
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PMID:Regulation of cyclooxygenase expression in the kidney by dietary salt intake. 953 Feb 64


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