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  • 1
    Electronic Resource
    Electronic Resource
    EFFECT OF INHIBITORS AND THE MECHANISMS OF ANION TRANSPORT IN THE PROXIMAL RENAL TUBULE OF RATS (1980)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 341 (1980), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1980.tb47164.x
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  • 2
    Electronic Resource
    Electronic Resource
    Transport of inorganic and organic substances in the renal proximal tubule (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 1165-1172 
    Details
    ISSN: 1432-1440
    Keywords: Epithelial transport ; Kidney ; Lactate transport ; Electrolyte transport ; Epithelialer Transport ; Niere ; Laktattransport ; Elektrolyttransport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Resorption bzw. Sekretion im proximalen Nierentubulus läuft einmal passiv auf dem parazellulären Weg, d.i. zwischen den Zellen hindurch, ab, zum anderen aktiv, transzellulär, durch die Zellen hindurch. Der transzelluläre aktive Transport ist in der Regel sekundär aktiv. Er verläuft gekoppelt an den Fluß von Na+-Ionen, wobei ein transzellulärer Gradient von Na+-Ionen, der seinerseits durch die kontraluminal gelegene (Na+-K+)-ATPase geschaffen wird, die Triebkraft liefert. Einmal in der Zelle, verlassen die Substanzen die kontraluminale Zellseite vermittels Karrier, die Na+-unabhängig sind. Mit Hilfe von Mikroperfusions- und elektrophysiologischen Techniken sowie mit Hilfe von Bürstensaumvesikeln wurde der Na+-Kotransport von Aminosäuren, Phosphat, Sulfat, Thiosulfat, Gallensäuren, aliphatischen und aromatischen Monokarboxylsäuren (Laktat) sowie der von Dikarboxylsäuren untersucht. Besonderes Augenmerk wurde dem bidirektionalen Transport von Thiosulfat sowie der Spezifität des Mono- und Dikarboxylsäure-Transportsystems gewidmet.
    Notes: Summary The transport through the epithelial cell layer of the renal proximal tubule proceeds in principle by passive paracellular and active transcellular transport. The active transcellular transport is mostly secondary active. This means it proceeds coupled with the flux of Na+ ions, where-by the transcellular gradient of sodium, created by the (Na++K+)-ATPase, located at the contraluminal cell side, provides the main driving force. Once in the cell the substances leave the other cell side by a Na+-independent, but carrier-mediated transport system. Using microperfusion and electrophysiological techniques as well as brush border membrane vesicle preparation the Na+-H+ countertransport and the Na+-cotransport of amino acids, phosphate, sulfate, thiosulfate, bile acids, aliphatic-aromatic monocarboxylic acids (lactate) and dicarboxylic acids was studied. Special emphasis will be given to the bidirectional transport of thiosulfate as well as to the specificity of the monocarboxylic acid and dicarboxylic acid transport system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716718
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  • 3
    Electronic Resource
    Electronic Resource
    Normal exocytosis and endocytosis of lysosomal β-hexosaminidase in a case of alpha1-antitrypsin deficiency (1983)
    Springer
    Journal of molecular medicine 61 (1983), S. 307-309 
    Details
    ISSN: 1432-1440
    Keywords: Alpha1-Antitrypsin deficiency ; β-Hexosaminidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Secretion of lysosomal β-hexosaminidase by cultivated skin fibroblasts and receptor-mediated endocytosis of leucocyte β-hexosaminidase from a patient by cultivated non-parenchymal rat liver cells and skin fibroblasts were similar to that of a control proband. The results suggest normal oligosaccharide side chains of high mannose type on lysosomal enzymes in alpha1-antitrypsin (AAT) deficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01497781
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  • 4
    Electronic Resource
    Electronic Resource
    Bicarbonate reabsorption in the papillary collecting duct of rats (1981)
    Springer
    Pflügers Archiv 389 (1981), S. 271-275 
    Details
    ISSN: 1432-2013
    Keywords: Adaptation, HCO 3 − transport ; Glycodiazine transport ; Metabolic acidosis ; Metabolic alkalosis ; Acetazolamide ; SITS ; Potassium deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using the technique of capillary perfusion and simultaneous luminal stop flow microperfusion the reabsorption of bicarbonate and glycodiazine from the papillary collecting duct was evaluated. Starting with equal H14CO 3 − and3H-glycodiazine concentrations in the luminal and peritubular perfusates, the decrease in the luminal concentration at 10 and 45 s contact time was measured. In control rats with 25 mmol/l HCO 3 − in the perfusates the rate of HCO 3 − reabsorption calculated from the 10 s values was 0.34 nmol cm−2s−1. In acute metabolic acidosis, the rate of bicarbonate reabsorption was 2,3 times higher. In metabolic alkalosis, the rate of bicarbonate absorption dropped to 13% of the control values. Also the 45 s values of acidotic and alkalotic animals differed significantly from each other. With 25 mmol/l glycodiazine in both perfusates the rate of biffer reabsorption as calculated from the 10 s values was 0.76 nmol cm−2s−1 in control rats and did not deviate significantly from this value in acidotic and alkalotic animals. In control rats the bicarbonate reabsorption in % was the same, no matter whether both luminal and capillary perfusate contained 25 mmol/l bicarbonate or 10 mmol/l. In acidotic rats the rate of HCO 3 − reabsorption did not change significantly if all Na+ in the perfusates was replaced by choline (0.88 versus 0.79 nmol cm−2s−1 at 25 mmol/l HCO 3 − ). When in acidotic rats 0.1 mmol/l acetazolamide or 1 mmol/l SITS (4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid) was added to both perfusates the rate of HCO 3 − reabsorption dropped by 75 and 58%, respectively. A potassium deficient diet for one week and DOCA administration had no influence on the bicarbonate reabsorption of rats which were on standard diet. The data indicate that (1) the buffer reabsorption from the papillary collecting duct is rather due to H+ ion secretion than to buffer anion reabsorption. (2) The adaptation to metabolic acidosis and alkalosis is specific for bicarbonate and not seen with glycodiazine. (3) Within the concentration range tested the HCO 3 − reabsorption rises linearly with the HCO 3 t- concentration. (4) The HCO 3 − reabsorption in the papillary collecting duct is Na+-independent, it can be inhibited by acetazolamide and SITS, but is not influenced by K+-deficient diet plus DOCA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584789
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  • 5
    Electronic Resource
    Electronic Resource
    A stopped flow capillary perfusion method to evaluate contraluminal transport parameters of methylsuccinate from interstitium into renal proximal tubular cells (1984)
    Springer
    Pflügers Archiv 400 (1984), S. 250-256 
    Details
    ISSN: 1432-2013
    Keywords: Kidney cortex structure ; Tissue compartments ; Transport models ; Inhibitory kinetics ; Facilitated diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to study the transport of dicarboxylic acids through the contraluminal cell membrane of proximal tubular cells,3H-methylsuccinate has been synthetized by catalytic hydration of methylfumarate. As the chromatography of radioactive material excreted in the urine after i.v. injection of3H-methylsuccinate shows, no metabolite is detectable during the first 3 min. After 10 min, less than 10% of the excreted radiolabel is metabolized. To measure the contraluminal influx of3H-methylsuccinate from the interstitium into cortical tubular cells, the renal vessels were clamped so that the proximal tubular lumina collapsed. Then Ringer solution was injected into the blood capillaries. It contained different concentrations of3H-methylsuccinate and14C-inulin as extracellular space marker. After contact times between 1 and 10 s, this fluid was withdrawn from the capillaries and the disappearance of3H-methylsuccinate relative to14C-inulin was measured. The morphological compartments in the outer cortex of the clamped glutaraldehyde-fixed kidney were evaluated by a stereological method. For proximal tubular cells a ratio of extracellular water space to intracellular space of 1:3.1 and a ratio extracellular water space to free cell water space of 1:2 was found. It was tested whether the experimental disappearance curves with 4 different starting concentrations of3H-methylsuccinate fit with the data from four model calculations. It was found that the data and the conditions of transport are consistent with the predictions of a facilitated diffusion model. In this model, a transport coefficient occurs which depends on the concentration of3H-methylsuccinate following saturation kinetics. The calculated parameters wer:K m for3H-methylsuccinate=0.12 mmol/l,J max=0.50 pmol/s ·cm (related to tubular length in cm). Furthermore, equations are given to calculate inhibitory constantsK i of competing dicarboxylic acids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00581555
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  • 6
    Electronic Resource
    Electronic Resource
    Contraluminal sulfate transport in the proximal tubule of the rat kidney (1984)
    Springer
    Pflügers Archiv 402 (1984), S. 264-271 
    Details
    ISSN: 1432-2013
    Keywords: Epithelial transport ; Contraluminal cell membrane ; Anion exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to study contraluminal sulfate transport the influx rate of35SO 4 2− from the interstitium into cortical tubular cells has been determined. Preloading of the rat with sulfate augmented contraluminal35SO 4 2− influx; preperfusion with sulfate-free solutions diminished it. The contraluminal35SO 4 2− influx in sulfate-loaded animals followed two parameter kinetics (K m 1.4 mmol/l,J max 1.2 pmol·s−1·cm−1). The contraluminal35SO 4 2− influx (starting concentration 10 μmol/l) did not change when the K+ concentration was varied between 4 and 40 mmol/l and the Ca2+ concentration from zero to 3 mmol/l. Omission of Na+ from the perfusates augmented contraluminal35SO 4 2− influx markedly. The increase is larger at pH 6 than at pH 7.4. Changes of pH affect contraluminal35SO 4 2− influx only when the solutions are Na+- and K+-free. Under these conditions the35SO 4 2− influx decreased when the ambient pH was raised from pH 6.0 to pH 8.0. Thiosulfate, selenate, molybdate, oxalate, phosphate, arsenate, and bicarbonate exerted competitive inhibition, while formate, 2-oxoglutarate and paraaminohippurate showed a biphasic response: inhibition at 50 mmol/l, no inhibition at 150 mmol/l. Chloride and bicarbonate inhibited35SO 4 2− influx at 10 μmol/l35SO 4 2− , but augmented sulfate influx at 5 mmol/l35SO 4 2− concentration in rats not preloaded with sulfate. The data indicate the presence of a contraluminal sulfate transport system which is shared by a variety of inorganic and organic anions. The biphasic behaviour of some anions suggests parallel pathways leading to a cis-inhibition at small and trans-stimulation at high anion concentrations. Na+ and H+ may be cotransported or interact with the transport system at a modifier site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00585509
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  • 7
    Electronic Resource
    Electronic Resource
    Reabsorption of monocarboxylic acids in the proximal tubule of the rat kidney (1982)
    Springer
    Pflügers Archiv 395 (1982), S. 212-219 
    Details
    ISSN: 1432-2013
    Keywords: SITS ; Probenecid ; Phloretin ; Acetazolamide ; Lactate ; Renal tubule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The transport ofd-lactate across the epithelium of the late proximal convolution was investigated by two methods: 1. by measuring the zero net flux transtubular concentration difference (Δc tt,45s) and the permeability (P) ofd-lactate and calculating from both the transtubular active transport rate (J lac act ). 2. By measuring the 3.5 s efflux ofd-lactate from the tubular lumen, while blood was flowing through the capillaries. The 3.5 s efflux comprises two components, one going through the brush border (J lac bb ) and one going the paracellular pathway (J lac paracell =P lac·c lac lumen). Both,J lac act andJ lac bb ofd-lactate gave the sameK m 1.9 and 1.7 mmol/l and the same maximal transport rate 3.2 and 2.9 pmol cm−1 s−1. TheK i ofl-lactate tested againstJ lac act andJ lac bb ofd-lactate was also the same: 1.1 and 1.0 mmol/l. These data indicate that under our experimental conditions only the flux through the brush border seems to be rate limiting and thatd-lactate uses the same transport system asl-lactate. When Na+ was omitted from the perfusatesJ lac act disappeared completely, whileJ lac bb was reduced by 64%. These data reflect the Na+ dependence of thed-lactate transport through the brush border. Variation of intra-and extracellular pH by raisingpCO2, omitting HCO 3 − from the perfusates or adding acetazolamide had no effect on the transport ofd-lactate when α-ketoglutarate was used as fuel. However, when acetate was used as fuel, intracellular acidosis brought the reducedJ lac act back to the values obtained with α-ketoglutarate as fuel. It is suggested that this is an effect on a contraluminal transport step. Probenecid (5 mmol/l) and phloretin (0.25 mmol/l) inhibitedJ lac act significantly.J lac bb , however, was only inhibited by probenecid when acetate was used as fuel. These data indicate that both compounds act on thed-lactate exit at the contraluminal cell side, but that probenecid acts in addition at the luminal cell side. SITS (1 mmol/l) augmentedJ lac bb when acetate was used as fuel and is similar to the effect of lowering intracellular pH as described above. The SH reagents mersalyl (1.0 mmol/l) and maleolylglycine (1 mmol/l) did not influenceJ lac bb .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584812
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  • 8
    Electronic Resource
    Electronic Resource
    Active sulfate reabsorption in the proximal convolution of the rat kidney: Specificity, Na+ and HCO 3 − dependence (1980)
    Springer
    Pflügers Archiv 383 (1980), S. 159-163 
    Details
    ISSN: 1432-2013
    Keywords: Renal tubule ; Sulfate transport ; Na+ coupled transport ; Thiosulfate ; Molybdate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using the standing droplet technique in the proximal convolution and simultaneous microperfusion of the peritubular capillaries, the decrease in luminal sulfate concentration with time and the zero net flux transtubular concentration difference of sulfate ( $$\Delta c_{{\text{SO}}_{\text{4}}^{{\text{2 - }}} } $$ ) at 45 s was determined — the latter being taken as a measure of the rate of active sulfate reabsorption. Starting with 0.5 mmol/l sulfate in both perfusates the $$\Delta c_{{\text{SO}}_{\text{4}}^{{\text{2 - }}} } $$ value of 0.35 mmol/l was approached exponentially with a half value time of 4.3 s. The $$\Delta c_{{\text{SO}}_{\text{4}}^{{\text{2 - }}} } $$ values in the early proximal and late proximal convolution did not deviate from each other. If the Na+ concentration in the perfusates was reduced, the $$\Delta c_{{\text{SO}}_{\text{4}}^{{\text{2 - }}} } $$ approached zero and extrapolated to a slightly negative value (c i〉c o). When 1 mmol/l ouabain was added to the perfusates $$\Delta c_{{\text{SO}}_{\text{4}}^{{\text{2 - }}} } $$ decreased by 66% (the latter experiments were performed in the golden hamster which is more sensitive to ouabain than the rat). 1 mmol/l thiosulfate diminished $$\Delta c_{{\text{SO}}_{\text{4}}^{{\text{2 - }}} } $$ by 68% and 1 mmol/l molybdate by 24%. Omitting or replacing bicarbonate by HEPES or glycodiazine reduced the sulfate reabsorption significantly, while acetazolamide (0.1 mmol/l) and increasing the CO2-pressure from 4.66 to 14.0 kPa (i.e. 5–15% CO2) had no effect. SITS 1 mmol/l had no effect on sulfate reabsorption. The data indicate that the sulfate reabsorption is driven by a Na+ gradient and inhibited by thiosulfate and molybdate, i.e. molecules which have a similar tetrahedral molecule structure. The sulfate reabsorption depends in an undefined manner on the presence of bicarbonate ions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00581877
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  • 9
    Electronic Resource
    Electronic Resource
    A cytotoxin of pseudomonas aeruginosa acts directly on the cortical thick ascending limb of henle's loop of rabbit kidney (1982)
    Springer
    Pflügers Archiv 394 (1982), S. 271-273 
    Details
    ISSN: 1432-2013
    Keywords: Pseudomonas aeruginosa toxin ; thick ascending limb of the loop of Henle ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examines directly the effect of a cytotoxin of Pseudomonas aeruginosa on the in vitro perfused rabbit cortical thick ascending limb of the loop of Henle (cTAL). 25 cTAL segments were perfused at high rate. The open circuit transepithelial electrical PD (PDte) and the specific electrical transepithelial resistance (Rt) were recorded continuously. From PDte/Rt the equivalent short circuit current (Isc) was calculated. The Isc was 214±30 μA·cm−2 under control conditions, and decreased significantly to 74±34 μA·cm−2 60 s after the addition of toxin (2 mg·l−1) to the lumen perfusate. Microscopic observation and photographs taken at that time clearly indicated swelling of the cTAL cells. Thereafter inhibition of active transport proceeded further, Rt fell progressively, and cells started to desquamate from the basement membrane. This effect of the toxin was dose dependent, and was half maximal at approximately 1.2 mg·l−1. From the bath side the effect was less marked and higher doses of toxin had to be used (half maximal effect at 5 mg·l−1). We conclude that this toxin of Pseudomonas aeruginosa exerts its toxic effect on the cTAL segment by increasing primarily the permeability of the lumen membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00589103
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  • 10
    Electronic Resource
    Electronic Resource
    Reabsorption of monocarboxylic acids in the proximal tubule of the rat kidney (1982)
    Springer
    Pflügers Archiv 395 (1982), S. 220-226 
    Details
    ISSN: 1432-2013
    Keywords: Na+-dependent transport ; d-Lactate transport ; Small fatty acids ; 3-Hydroxybutyrate ; Acetoacetate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 3.5 s efflux ofd-lactate (1 mmol/l) injected in the lumen of the late proximal convolution as well as the zero net flux transtubular concentration difference ofd-lactate, which is a measure of its active transtubular transport rate, were determined. The inhibitory potency of small fatty acids and their analogs added to the perfusate in a concentration of 10 mmol/l on both, the 3.5 s efflux and in most cases also the 45 s transtubular concentration difference ofd-lactate was measured. It was found that 1. small fatty acids from acetate to octanoate inhibit 3.5s efflux ofd-lactate, the largest inhibition being exerted by propionate and butyrate. With increasing chain length the inhibitory potency decreased and disappeared with decanoate. 2. Considering the acetate-, propionate- and butyrate analogs, introduction of an electron attracting group such as Cl, Br, I, CN, SH, N3 on C atom 2 increased the inhibitory potency, compared to the unsubstituted fatty acid. An OH on C2 increased or did not change the inhibition while an OH on C atom 3 reduced or blunted the inhibition. A keto-group, as it is present in glyoxylate prevented inhibition, but pyruvate inhibited to the same extent as lactate, and acetoacetate was even more inhibitory than 3-hydroxybutyrate. Cl substitution on C3 preserved the strong inhibitory potency, while 4-Cl butyrate, was only sparsely inhibitory. A NH 3 + group at any position precludes inhibition. 3. As seen with Cl or OH substituted propionate and butyrate the inhibitory potency increased with decreasingpK a of the compounds. 4. Increasing the chain length by a CH3 as from acetate to propionate, from glycolate to lactate and also from glyoxylate to pyruvate increased the inhibitory potency. 5. When tested against the 3.5 s efflux ofl-lactate, the same inhibitory pattern was seen as withd-lactate. 6. The transport of chloroacetate, glycolate and acetoacetate, which were available in a radio-labeled form of high specific activity, was measured directly in 3.5 s efflux studies. It was Na+-dependent and could be inhibited by 10 mmol/ll-lactate. Glyoxylate, on the other hand, which did not inhibitd-lactate transport, did also not show a Na+-dependent,l-lactate inhibitable efflux from the tubular lumen. The data indicate that a variety of short chain fatty acids and their analogs are transported by the same Na+-dependent transport system in the brush border which transportsl- andd-lactate. The specificity is determined by the molecule size, hydrophobicity of one part of the molecule, the electron attracting abilities of substitutes on C-atom 2 or 3 and the charge distribution on the molecule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584813
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