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

We examined the hypothesis that proton-potassium-activated adenosine triphosphatase (H-K-ATPase) mediates K absorption and acidification in the inner stripe of the outer medullary collecting duct (OMCDi). Rabbits were fed a low-K diet (0.55% K) for 7-14 d because we have demonstrated previously that this low-K diet stimulates K-absorptive flux by the OMCDi. Proton secretion was measured as net total CO2 flux (JTCO2) by microcalorimetry. After basal collections, either vehicle or an inhibitor of gastric H-K-ATPase, omeprazole (0.1 mM), was added to the perfusate during the second period. Addition of vehicle to the perfusate changed neither the transepithelial voltage (VT, in millivolts) nor the JTCO2. In contrast, the addition of omeprazole (0.1 mM) to the perfusate abolished JTCO2 (from 14.5 +/- 5.6 to -0.1 +/- 3.1 pmol.mm-1.min-1) without significantly affecting VT. In additional experiments, in 16 tubules there was significant net K absorption (JK) of 5.0 +/- 1.0 pmol.mm-1.min-1 during the basal period, which exceeded the rate of K absorption that could be attributed to a paracellular voltage-mediated pathway (JKP = 1.0 +/- 0.4 pmol.mm-1.min-1, P less than 0.01). Administration of vehicle did not significantly affect either VT or JK. However, omeprazole abolished JK (from 5.1 +/- 1.0 to 0.1 +/- 2.5 pmol.mm-1.min-1) without affecting VT or JNa. The present results demonstrate that the OMCDi possesses an active, omeprazole-sensitive acidification and K-absorptive mechanism. These findings are consistent with the presence of H-K-ATPase activity in this nephron segment.
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PMID:Active proton secretion and potassium absorption in the rabbit outer medullary collecting duct. Functional evidence for proton-potassium-activated adenosine triphosphatase. 254 29

The regulation of proton transport and cytosolic pH was studied in rat papillary collecting duct (PCD) cells in culture using a pH-sensitive fluorescence probe, 2,7-bis-carboxyethyl-5,6-carboxyfluorescein (BCECF). Data were obtained from confluent monolayers grown on glass coverslips and dipped in a HCO3- -free medium, pH 7.40. The resting intracellular pH (pHi) was 7.16 +/- 0.03 (n = 20). When PCD cells had been acidified by pretreatment with NH4Cl, pHi immediately recovered toward the resting value. Two mechanisms participated in this recovery: a Na+-dependent mechanism which could be inhibited by amiloride (indicative of Na+-H+ exchanger) and a Na+-independent process (a proton ATPase). The pHi recovery from acid loading was inhibited by amiloride to about 55% of the control recovery (half-maximal effect at 100 microM). The rate of pHi recovery after the readdition of Na+ to a sodium-free medium exhibited saturation kinetics (half maximal rate at 28 mM). Dicyclohexylcarbodiimide (DCCD), an inhibitor of a plasma membrane proton ATPase, and the depletion of cellular ATP induced by 2 mM potassium cyanide (KCN) also partially inhibited the rate of pHi recovery after cell acidification with a NH4Cl load. When PCD cells were treated with 1 mM DCCD, amiloride almost completely inhibited pHi recovery. Amiloride and the removal of external Na+ had induced a gradual fall in pHi to a new resting value and rapidly recovered when Na+ was added. We conclude that PCD cells grown in culture have at least two proton transport mechanisms: a Na+-H+ exchanger and a plasma membrane proton ATPase. The kinetics of these processes can be reliably assessed by the pH-sensitive fluorescent probe, BCECF. Both the Na+-H+ exchanger and the plasma membrane proton ATPase may contribute to urinary acidification.
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PMID:Dual regulatory mechanisms of proton transport in rat papillary collecting duct cells in culture. 255 3

To examine the cellular mechanisms of H+ transfer in rabbit papillary collecting duct (PCD), the 5,5-[14C]dimethyloxazolidine-2,4-dione-derived cell pH (pHi), the [3H]triphenylmethylphosphonium-derived membrane potential (Em), the lumen-to-cell Na+ concentration gradient [( Na+]o/[Na+]i), and cell potassium and chloride concentrations were studied at 37 degrees C in separated PCD from rabbits pretreated with deoxycorticosterone acetate. The variations in cell pH values were used as an index of changes in H+ secretion. Under standard conditions pHi was 7.30 +/- 0.04, [Na+]o/[Na+]i was 2.46 +/- 0.43, Em was 78 +/- 7 mV (cell negative), [K+]i was 105 +/- 10 mM, and [Cl-]i was 33 +/- 6 mM; the value of pHi thus remained higher than expected if H+ ions were passively distributed (6.13). Acetazolamide, 10(-4) M, alkalinized the cells. When [Na+]o/[Na+]i was reduced (low-Na+ medium or 10(-3) M ouabain), the cells did not acidify, suggesting that net H+ secretion did not decrease; also, pHi was not linked to the variations in the transmembrane chloride concentration gradients. When the cells were depolarized (low-Na+ medium), they became more alkaline; when the cells were hyperpolarized (10(-4) M amiloride), they became more acid; minor change in Em (ouabain) was associated with no change in pHi. It is concluded that: 1) H+ is actively secreted into the lumen; 2) active H+ secretion may not be secondary, via electroneutral Na+:H+ countertransport or HCl cotransport, but probably occurs via a primary H+ pump; 3) variations in Em probably affect pHi by acting on both the active H+ transport system and passive movements of HCO-3 (or its equivalent).
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PMID:Hydrogen transport in papillary collecting duct of rabbit kidney. 257 70

The present study quantitated the effects of extracellular volume expansion on sodium and water excretion in 118 anesthetized dogs. The animals received a priming injection of 10 ml kg-1 Ringer solution i.v. which was followed by a constant Ringer solution infusion at a rate of 0.25 ml.min-1.kg-1 until the end of the experiment. Fifteen minutes after the start of the constant infusion the renal parameters were examined in 11 subsequent 15 min periods (the total time was 3 hours). Volume expansion produced no significant change in arterial blood pressure, glomerular filtration rate (GFR), plasma sodium and potassium concentration or, haematocrit, but did reduce the CPAH from 284 ml.min-1 to 218 ml.min-1 (the data were calculated for 100 gram wet kidney weight). There were constant significant increases in the urinary excretion rate from 0.84 ml.min-1 to 4.06 ml.min-1 and the 39% of the infused water was excreted during the experiment. Volume expansion also caused a significant increase in sodium excretion during the three first periods from 120 mumol.min-1 to 329 mumol.min-1 followed by a small but significant decrease. The sodium excretion at the end of the experiment was 221 mumol.min-1 and the 23% of the infused sodium was excreted in the course of the experiment. The increase of the water excretion during the volume expansion was associated with fall of the urine osmolality and the urine because hypoosmotic as compared to the plasma. We have provided evidence that vasopressin was not involved in the control of water excretion in our experiments. It is concluded that neither filtered sodium nor decreased aldosterone secretion can account for the increase in sodium excretion that occurs after Ringer solution loading in the dog. It has been proposed that a decrease in plasma protein concentration may decrease passive sodium reabsorption due to oncotic forces in the proximal tubule. The Ringer solution diuresis elicits a rise in medullary blood flow, thereby causing a washout of medullary sodium. This might dissipate the osmotic force for the back-diffusion of water from the collecting duct. Our studies indicate that the response of the diluting segments of the distal nephron to increased delivery of sodium depends upon the presence or absence of volume expansion. However the increase of the distal tubular loading activates the tubuloglomerular feedback which increases the proximal tubular reabsorption. Based on these assumptions our studies provide further evidence that the tubuloglomerular feedback regulates the blood pressure in the peritubular capillaries in the cortex around the proximal tubules.
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PMID:The effect of Ringer solution induced extracellular volume expansion on kidney function. 260 31

Sodium, phosphorus, chloride and potassium concentrations were measured by a new method in individual principal and intercalated cells in the cortical collecting duct in vitro. Electron microprobe analysis was applied to freeze-dried cryosections of the isolated perfused rabbit cortical collecting duct. Cell analyses were performed under control conditions and after addition of ouabain to the bath. Under control conditions similar sodium, potassium, chloride, and phosphorus concentration (means +/- SEM) were observed in principal (10.0 +/- 0.6, 126.5 +/- 2.7, 24.6 +/- 1.0, and 121.5 +/- 3.5 mmol/kg wet weight, respectively) and intercalated cells (9.0 +/- 0.9, 127.1 +/- 4.2, 27.4 +/- 1.8, and 118.7 +/- 4.9 mmol/kg wet weight, respectively). In principal cells ouabain (10 min) caused an increase in sodium and chloride concentrations by 104 and 13 mmol/kg wet weight, and a decrease in potassium and phosphorus concentrations by 106 and 32 mmol/kg wet weight. These changes in cell element concentrations can be ascribed to an exchange of intracellular potassium against extracellular sodium and to cell swelling due to influx of extracellular fluid. The effects of ouabain on intercalated cells were far less pronounced than on principal cells. This different susceptibility to ouabain of principal and intercalated cells can be ascribed to differences in active and passive transmembrane ion transport pathways.
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PMID:Effect of ouabain on electrolyte concentrations in principal and intercalated cells of the isolated perfused cortical collecting duct. 272 28

Lactate production and ion fluxes were measured in isolated rat papillary collecting duct cells (PCD) to gain further insight into the transport properties of the papillary collecting duct. Lactate production was found to be inhibited by bumetanide in a dose-dependent manner, a maximum inhibition of 22% was obtained at 10(-4) M bumetanide and an apparent Ki of 10(-8) M was determined. Bumetanide inhibition of lactate production was dependent on the presence of sodium and chloride. Chloride removal inhibited lactate production also by 20%. Bumetanide (10(-4) M) inhibited by 35% sodium uptake into PCD cells exposed to 10 mM ouabain and chloride uptake into ion depleted PCD cells by 40%. In addition, this bumetanide-sensitive chloride uptake was dependent on the presence of sodium and potassium in the incubation medium. Furthermore, 86Rb uptake into these cells was significantly reduced in the presence of 10(-4) M bumetanide. These data provide evidence for the operation of a Na-K-Cl cotransport system in rat papillary collecting duct cells. This transport system might be involved in active chloride transport in the papillary collecting duct and/or volume regulation of the PCD cells.
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PMID:A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells. 277 93

The ionic conductive properties were studied of epithelia of collecting duct principal cells which had been grown in primary tissue culture from renal cortex/capsule explants. When pretreated with aldosterone (10(-6) mol/l) and bathed on either surface with isotonic HCO3(-)-free Ringer's solution, the transepithelial voltage, Vte, varied between -21 and -72 mV (apical surface negative) while the transepithelial resistance, Rte, ranged from 0.4 to 1.5 k omega cm2. By 10:1 step-changes in Na+ concentration the apical cell membrane was shown to have a high conductivity for sodium, inhibitable by amiloride, 10(-6) mol/l. However, contrary to observations in natural collecting duct under control conditions, amiloride never reversed the polarity of Vte even at 10(-4) mol/l. Both the apical and the basolateral cell membranes were conductive for potassium and both conductivities were inhibitable by Ba2+ (5 mmol/l). 10:1 reduction of apical Cl- concentration strongly hyperpolarized Vte with a monophasic time course suggesting the presence of a paracellular shunt conductance for Cl-. In addition there may be a small Cl- conductance present in the apical cell membrane since apical application of the chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPAB) at 10(-7) mol/l produced a minute but significant hyperpolarization. On the other hand, 10:1 reduction of basolateral Cl- concentration caused a biphasic change in Vte (initial depolarization, followed by repolarization) which indicates the presence of a large Cl- conductance in the basolateral cell membrane. The latter was not inhibitable by 10(-7) mol/l NPPAB. Higher concentrations of this and of an other Cl-channel blocker produced non-specific effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ionic conductances of cultured principal cell epithelium of renal collecting duct. 284 58

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


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