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)

Amiloride, triamterene, and the spirolactones are potassium-sparing diuretics which act on the distal parts of the nephron, from the late distal tubule to the collecting duct. In these segments, active sodium reabsorption occurs through the following mechanism: sodium ions enter the cell through specific channels present in the luminal membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase. Amiloride in micromolar concentrations reduces the sodium transport by blocking the luminal membrane sodium channel. Triamterene has a similar effect, although with a lower affinity; the available studies do not allow to determine if an inhibitory effect of triamterene on the Na-K-ATPase plays an additional role in its diuretic action. The spirolactones are competitive inhibitors of aldosterone, the mineralocorticoid hormone which promotes sodium reabsorption by increasing both the number of active sodium channels in the luminal membrane and the number of active Na-K pumps in the peritubular membrane. By the inhibitory effect on the electrogenic sodium transport, amiloride, triamterene, and the spirolactones decrease the lumen-negative transepithelial potential difference. This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion.
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PMID:Potassium-sparing diuretics. 245 8

The inner medullary collecting duct (IMCD) effects net sodium reabsorption under the control of volume regulatory hormones, including atrial natriuretic peptides (ANP). These studies examined the mechanisms of sodium transport and its regulation by ANP in fresh suspensions of IMCD cells. Sodium uptake was inhibited by amiloride but insensitive to furosemide, bu-metanide, and hydrochlorthiazide. These results are consistent with uptake mediated by a sodium channel or Na+/H+ exchange. To determine the role of sodium channels, cells were hyperpolarized by preincubation in high potassium medium followed by dilution into potassium-free medium. Membrane potential measurements using the cyanine dye, Di(S)-C3-5 verified a striking hyperpolarization of IMCD cells using this protocol. Hyperpolarization increased the apparent initial rate of sodium uptake fourfold. Amiloride and ANP inhibited potential-stimulated sodium uptake 73% and 65%, respectively; the two agents together were not additive. Addition of 5 mM sodium to hyperpolarized cells resulted in a significant amiloride-sensitive depolarization. Half-maximal inhibition of potential-driven sodium uptake occurred at 3 X 10(-7) M amiloride, and 5 X 10(-11) M ANP. We conclude that sodium enters IMCD cells via a conductive, amiloride-sensitive sodium channel, which is regulated by ANP. ANP inhibition of luminal sodium entry in the IMCD appears to contribute to the marked natriuretic effect of this hormone in vivo.
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PMID:Atrial natriuretic peptides inhibit conductive sodium uptake by rabbit inner medullary collecting duct cells. 245 85

Taking into account recent results obtained with isolated papillary collecting duct cells the metabolic pathways and membrane transport systems of collecting duct cells are reviewed. The plasma membranes contain a luminal proton AT-Pase and a contraluminal Cl-/HCO3- exchanger which are involved in proton secretion; a luminal sodium channel and a contraluminal Na+/K+-AT-Pase for sodium reabsorption; a K+ channel for potassium secretion, and a Na+/K+/Cl- cotransport system for chloride transport and/or volume regulation. The plasma membranes also possess transport systems for organic substrates and organic osmolytes. D-glucose, the main substrate of the papillary collecting duct is taken up into the cell by a sodium-independent D-glucose transport system with a Km of 1.2 mM. The plasma membrane also contains mechanisms which mediate sorbitol release into the medium. This mechanism is stimulated when cells are exposed to media with a low osmolality and inhibited when cells are exposed to media with a high osmolality. D-glucose is used as metabolic substrate in anaerobic and aerobic glycolysis and as precursor for sorbitol synthesis via the aldose reductase, which is highly enriched in papillary collecting duct cells. The cells also show gluconeogenic activity as evidenced by incorporation of labeled carbon from L-alanine into glycerol, sorbitol, and myo-inositol. Accordingly, the cells show fructose-1,6-biphosphatase activity. Sorbitol synthesis in contrast to sorbitol permeability is not affected by osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Transport mechanisms and metabolic processes in isolated cells of the collecting tubule of the kidney papilla]. 284 46

Mineralocorticoids play a major role in the regulation of sodium transport in a variety of tissues, including the cortical collecting duct (CCD) of the mammalian nephron. To assess, in part, the underlying mechanism(s) of this control, the present studies were designed to evaluate, first, the influence of mineralocorticoids on the Na-K-ATPase activity in the rabbit CCD and, secondly, a possible role of sodium entry into the cell at the luminal border on the regulation of the Na-K-ATPase. In the first series of studies, rabbits were maintained on a low sodium diet which raised serum aldosterone levels from 16 to 70 ng/dl after 3-4 days, with further elevations being expressed with treatment for two weeks or more. In CCDs isolated from these animals, the Na-K-ATPase increased from 13 to 40 pmol ADP min-1 mm-1 after 3-4 days on the low sodium regimen, but then declined, returning to control values after approximately 2 weeks. This decline in activity was preceded by a decrease in the Na+ concentration of the urine to low levels and hence, likely coincided with a decreased delivery of sodium to, and sodium entry into the cells of, the CCD. If dietary manipulations were used to maintain a high delivery of sodium to the CCD in the animal, elevation of plasma mineralocorticoid levels by treatment with deoxycorticosterone acetate (DOCA) caused a similar elevation in the Na-K-ATPase activity after 3-4 days, which did not decline with continued treatment for up to 2 weeks. Furthermore, it was observed that mineralocorticoids only exerted their effect on the Na-K-ATPase after a latent period of 1 day, well after sodium excretion had fallen, indicating that sodium entry into the CCD cells was already stimulated. If animals were simultaneously treated with DOCA and the sodium channel blocker amiloride for 3-4 days, the effects on the Na-K-ATPase were markedly reduced, whereas amiloride treatment alone had no effect on the enzyme activity. Since others have shown that mineralocorticoids induce synthesis of the Na-K-ATPase subunits in toad bladder cells in an amiloride-insensitive manner, sodium must be exerting its effect on a process after translation. It is concluded that the initial effect of mineralocorticoids in the CCD is on sodium entry with a delayed induction of the Na-K-ATPase, which is regulated by Na-dependent modulation of a posttranslational process.
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PMID:Sodium-dependent modulation of the renal Na-K-ATPase: influence of mineralocorticoids on the cortical collecting duct. 298 28

Previously, it has been shown that the addition of bradykinin (Bk) to M-1 cortical collecting duct cells in the presence of endothelial cells decreased short-circuit current (Isc), a measure of net active transport. This effect is presumably due to the release of endothelium-derived nitric oxide (EDNO), because the decrease in Isc could be blocked with Nw-nitro-L-arginine. To show that the inhibition of Isc was due to EDNO rather than prostaglandins, the ability of a cyclooxygenase inhibitor to block the inhibition was examined. When Bk was added to cocultures in the presence of meclofenamate (10(-5) M), Isc decreased from 62 +/- 12 to 44.5 +/- 7 muA/cm2, not significantly different from that in the absence of meclofenamate. To determine if the effect was due to an alteration of sodium absorption, Bk (10(-9) M) was added to cocultures, resulting in a decrease in Na flux from 28 +/- 3.1 to 20 +/- 2.2 nEq/min (P < 0.05), with Isc decreasing from 25 +/- 2.4 to 20 +/- 3.6 nEq/min (P < 0.05). To examine if the inhibition was due to blockade at the apical membrane sodium channel or the basolateral Na+/K+ ATPase, the cation-selective ionophore nystatin was used. Nystatin reversed the effect of EDNO on Isc. The effects of EDNO on Na+/K+ ATPase were also measured directly. Under maximum rate conditions, the Na+/K+ ATPase activity of control and Bk-treated cocultures was 5.2 +/- 0.3 and 6.8 +/- 1.0 nmol/min per square centimeter, respectively (not significantly different).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial-derived nitric oxide inhibits sodium transport by affecting apical membrane channels in cultured collecting duct cells. 791 34

Sodium transport across the apical membrane, via amiloride sensitive sodium channels, is the limiting step of sodium absorption in transporting epithelia with high intercellular electrical resistance, such as the distal parts of the colon and of the renal tubule. Several types of amiloride sensitive sodium channels have been functionally characterized: one of them (type I) with high selectivity and low conductance for sodium is under the control of aldosterone and antidiuretic hormone. This channel has been cloned (2): it is formed of three subunits, alpha, beta and gamma. The distribution of these subunits has been examined in several epitheliums at the mRNA (in situ hybridization) and protein (immunocytochemistry) levels. All three subunits are expressed in the most superficial cells of the distal colon, in principal cells of the renal distal tubule and cortical collecting duct, in striated ducts of serous acini of salivary glands, and in excretory ducts of sweat glands. Immunocytochemistry established the apical localization of the channel subunit proteins. No expression was detected in other cell types of these tissues. These results highlight the crucial role of the type I amiloride sensitive sodium channel in the control of sodium homeostasis at the level of tight, aldosterone-sensitive epitheliums. Furthermore, novel questions are opened, in view of the sodium channel being a member of a highly conserved family of mechanoreceptors, and of its implication in some human genetic diseases.
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PMID:[Distribution of amiloride-sensitive sodium channel in epithelial tissue]. 859 Feb 16

Three subunits (alpha, beta, gamma) of the amiloride-sensitive epithelial sodium channel have been recently characterized. The channel subunits have significant homologies with the Caenorhabditis elegans mec-4, mec-10 and deg-1 genes, which are involved in control of cell volume and mecanotransduction. These subunits are coexpressed at equivalent levels in the renal collecting duct and the distal colon epithelium which are high resistance sodium transporting epithelia. We have investigated whether these subunits were expressed, at the mRNA level, in transporting as well as non transporting epithelial cells of rat skin. In full-thickness abdominal skin only alpha and gamma subunit mRNAs were detected, while all three subunit mRNAs were present in sole skin, as demonstrated by RNase-protection assay. Furthermore, the level of expression of each subunit varied with the epithelial cell type as demonstrated by in situ hybridization: epidermal and follicular keratinocytes express mostly alpha and gamma subunits (while beta was low); a prevalence of beta and gamma was observed in sweat glands. Thus, it appeared that two out of the three subunit mRNAs predominated in each epithelial structure. In addition, mRNAs of the alpha, beta and gamma subunits of the amiloride-sensitive sodium channel were expressed at a higher level in large suprabasal epidermal keratinocytes (which undergo terminal differentiation) than in small proliferative basal keratinocytes.
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PMID:Differential expression of epithelial sodium channel subunit mRNAs in rat skin. 883 61

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

We have examined whether arginine vasopressin (AVP) can induce a long-term modulation of transepithelial ion transport in addition to its well known short-term effect. In the RCCD1 rat cortical collecting duct cell line, an increase in both short-circuit current and 22Na transport was observed after several hours of 10(-8) M AVP treatment (a concentration above the in vivo physiological range). This delayed effect was partially prevented by apical addition of 10(-5) M amiloride and was blocked by 10(-6) M actinomycin D and 2 x 10(-6) M cycloheximide. The amounts of mRNA encoding the alpha1 (not beta1) subunit of Na+/K+-ATPase and the beta and gamma (not alpha) subunits of the amiloride-sensitive epithelial Na+ channel were significantly increased by AVP treatment. The increase in mRNA was blocked by actinomycin D, not by amiloride, suggesting a Na+-independent increase in the rate of transcription of these subunits. The translation rates of the alpha1 subunit of Na+/K+-ATPase and the beta and gamma subunits of the rat epithelial sodium channel increased significantly, whereas the translation rates of the other subunits remained unchanged. Finally, the number of Na+ channels present in the apical membrane of the cells increased, as demonstrated by enhanced specific [3H]phenamil binding.
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PMID:Transcriptional regulation of sodium transport by vasopressin in renal cells. 940 70

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


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