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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 1165-1172 
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 395 (1982), S. 212-219 
    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
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 395 (1982), S. 220-226 
    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
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 395 (1982), S. 227-231 
    ISSN: 1432-2013
    Keywords: d-Lactate ; Benzoate ; Cinnamate ; Nicotinic acid ; Pyrazinoate
    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 was measured. This efflux can be divided into a Na+-dependent, saturable component flowing through the brush border and a Na+-independent non-saturable component flowing through the paracellular pathway. The inhibitory potency of benzoate and its analogs, of phenyl-substituted acetate-, propionate-and butyrate analogs, of cinnamate and analogs, of heterocyclic monocarboxylic acids and related compounds added to the perfusate in a concentration of 10 mmol/l was measured. It was found that 1. benzoate added in a concentration of 10 mmol/l to the luminal perfusate inhibits transport ofd-lactate, and the meta- and para-substituted analogs of benzoate inhibit in a fashion predicted by Hammett's theory. Side groups which withdraw electrons from the COOH group inhibit while substitutes who deliver electrons toward the reaction center do not. 2. Replacement of a hydrogen atom by a phenyl ring at the C2 atom of acetate, glycolate and glyoxylate does not change the inhibitory pattern of these substances ond-lactate transport. Replacement of a hydrogen atom on the C2 atom of propionate and lactate reduces the ability of these molecules to inhibitd-lactate transport. But replacement of a hydrogen atom at the C3 atom of propionate, pyruvate and lactate abolishes the inhibitory potency. Similarly the inhibitory potency decreases from butyrate 〉 2-phenylbutyrate 〉 3-phenylbutyrate 〉 4 phenylbutyrate. The latter two are actually no longer inhibitory. 3. Trans-cinnamate, cis-cinnamate (3-phenyl trans or cis acrylic acid) and 3-phenylpropiolate are also not inhibitory. But introduction of an electron attracting CN group on C2 atom of cinnamate evokes inhibitory potency. 4. The heterocyclic compounds nicotinic acid and pyrazinoic acid exert strong inhibition ond-lactate transport, while picolinic acid and isonicotinic acid exert only moderate inhibition. Nicotinic and pyrazinoic acid show also a secretory component in their transport behaviour. 5. If the COOH group of benzoate is replaced by a SO3H group (benzenesulfonic acid) or if a second ring is induced (1 or 2 naphthoic acid) the inhibitory potency is lost. 6. Amongst other organic anions which do not inhibitd-lactate transport are paraaminohippurate, urate, and taurocholate. The data indicate that a main determinant of the specificity of the Na+-dependent aliphatic aromatic monocarboxylic acid reabsorption system in the renal brush border is the electron density at the reaction center, i.e. the free carboxylic group. Furthermore, the size of the molecule and its hydrophobicity at one cell pole is limiting for its ability to react with the carrier.
    Type of Medium: Electronic Resource
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