Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Sodium Transport  (3)
  • Amiloride  (2)
  • Dicarboxylate transport  (2)
  • Electron-attracting groups  (2)
Collection
Publisher
  • 1
    ISSN: 1432-2013
    Keywords: Electron-attracting groups ; Electron-donating groups ; Hydrophobicity ; Amiloride ; Cimetidine ; N-methyl-4-phenylpyridinium (MPP+)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to evaluate whether N-containing substrates interact with the organic “anion” (p-aminohippurate, PAH) or only with the organic “cation” (N 1-methylnicotinamide, NMeN) transport system or with both, the stop-flow peritubular capillary microperfusion method was applied in the rat kidney in situ and the apparent K i values of several classes or organic substrate against contraluminal NMeN and PAH transport were determined. Organic “anion” and organic “cation” transport are in inverted commas because neither transporter sees the degree of ionization in bulk solution, and they also accept nonionizable substrates [Ullrich KJ, Rumrich G (1992) Pflügers Arch 421:286–288]. Amines must be sufficiently hydrophobic (phenylethylamine, piperidine, piperazine) in order to interact with NMeN transport. Additional Cl, Br, NO2 or other electronegative groups render them inhibitory towards PAH transport also. Such bisubstrate amines were identified as follows: metoclopramide, bromopride, diphenhydramine, bromodiphenhydramine, verapamil, citalopram, ketamine, mefloquine, ipsapirone, buspirone, trazodone, H7 and trifluoperazine. Imidazole analogues interact with both transporters if they bear sufficiently hydrophobic alkyl or aryl groups or electronegative sidegroups. Bisubstrate imidazole analogues are tinidazole, pilocarpine, clonidine, azidoclonidine and cimetidine. Pyridines and thiazoles interact with the NMeN transporter if they have an additional ring-attached NH2 group. Again with an additional Cl, Br, or NO2 group the aminopyridines and aminothiazoles also become inhibitors for the PAH transporter. Amongst the guanidines only substances with several electronegative side-groups such as guanfacine, amiloride, benzylamiloride and ranitidine, interact with both transporters. Amongst the phenylhydrazines only 4-bromophenylhydrazine interacts with the NMeN transporter and 4-nitrophenylhydrazine with both transporters. Quinoline (isoquinoline) and its amino and hydroxy analogues interact with both transporters, their pKa values correlate directly with the affinity to the NMeN transporter and reciprocally with their affinity to the PAH transporter. In experiments with labelled substrates only the sufficiently hydrophilic cimetidine, amiloride and ranitidine show a saturable transport, which can be inhibited by probenecid (apalcillin) and tetraethylammonium in an additive manner. The highly hydrophobic substrates verapamil, citalopram, imipramine, diltiazem and clonidine enter the cell very fast in an unsaturable and uninhibitable manner, apparently in the undissociated form, since N-methyl-4-phenylpyridinium, which — disregarding its ionization — is similarly hydrophobic, shows a transport behaviour similar to that of tetraethylammonium [Ullrich et al. (1991) Pflügers Arch 419:84–92]. Ethidium bromide and dimidium bromide, which have a permanent cationic quaternary nitrogen and two sufficiently electronegative NH2 groups, also interact with both transporters. The data indicate that a molecule qualifies as a bisubstrate if it carries both the essentials for organic anion (PAH) transport: hydrophobicity, sufficient acidity or electron-attracting O, OH, Cl, Br, NO2 groups, plus the essentials for organic cation transport: hydrophobicity, sufficient basicity or electron-donating N-containing groups. The nitrogen atoms in the N-containing molecules quinoline (pK a 4.9), isoquinoline (pK a 5.4) and benzylpyridine (pK a 5.13) are of such low basicity that they apparently can also interact with the PAH transporter. Apparent hydrophobicity (disregarding ionization) determines interaction with the transporters, while real hydrophobicity [log (octanol distribution values)] determines the diffusion through the lipid bilayer of the cell membrane.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-2013
    Keywords: Electron-attracting groups ; Electron-donating groups ; Hydrophobicity ; Corticosteroids ; Androstene analogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to test what chemical structure is required for a substrate to interact not only with the contraluminal organic anion (p-aminohippurate, PAH) transporter, but also with the organic cation (N 1-methylnicotinamide, NMeN, or tetraethylammonium, TEA) transporter, the stop-flow peritubular capillary perfusion method was applied and app. K i values were evaluated. Zwitterionic hydrophobic dipeptides not only interact with PAH but also with NMeN transport although with lower inhibitory potency (K i,PAH=0.2–1.4; K i,NMeN 614 mmol/l). Amongst the zwitterionic cephalosporins, which all inhibit PAH transport, the amino cephalosporin analogue cefadroxil was identified to interact also with NMeN transport (K i,PAH = 3.0, K i,NMeN=11.2 mmol/l). All Zwitterionic naphthyridine and oxochinoline gyrase inhibitors tested inhibit NMeN transport with app. K i,NMeN values between 1.2 mmol/l and 4.7 mmol/l; the naphthyridine analogues show a good inhibitory potency against PAH transport (K i,PAH ≈ 0.4 mmol/l), the piperazine-containing quinolone analogues have a moderate inhibitory potency (K i,PAH=1.1–2.5 mmol/l) and the piperazine-containing pipemidic acid did not inhibit PAH transport at all. Zwitterionic thiazolidine carboxylate phosphamides also interact with both transporters (app. K i,PAH ≈ 3.0; app. K i,NMeN ≈ 18.0 mmol/l). The nonionizable oxo- and hydroxy-group-containing corticosteroid hormones also interact with the two transporters. (a) An OH group in position 21 is necessary for interaction with the PAH transporter, but not for interaction with the TEA transporter. (b) Introduction of an OH group in position 17α abolishes interaction with the TEA transporter, but has different effects with the PAH transporter. (c) Introduction of an OH group in position 6 abolishes interaction with both, the PAH and the TEA transporter. (d) A change of the side-group in position 11 of corticosterone from -OH to -H to=O enhances interaction with the PAH transporter but has no effect on the interaction with the TEA transporter. Nonionizable 4- or 5-androstene analogues inhibit both transporters with app. K i between 0.16 mmol/l and 0.64 mmol/l, if the steroids are soluble in a concentration greater than 1 mmol/l. Nonionizable oxazaphosphorins with more than one chloroethyl group interact with the PAH transporter with app. K i between 0.84mmol/l and 4.9mmol/l and with the NMeN transporter with app. K i between 3.2 mmol/l and 18.7 mmol/l. Thus a substrate interacts with both transporters if it is sufficiently hydrophobic, possesses acidic and/or electron-attracting plus basic and/or electron-donating groups, or possesses several electron-attracting nonionizable groups (O, OH, Cl). A certain spatial arrangement of the interacting groups seems to be necessary.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-2013
    Keywords: Dicarboxylate transport ; Sulfate transport ; Benzoyl compounds ; Phenoxy compounds ; Valproate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to study the specificity of the contraluminal para-aminohippurate (PAH) transport system, the inhibitory potency of monocarboxylates on the3H-PAH influx from the interstitium into cortical tubular cells in situ has been determined. The following was found: if a homologous series of fatty acids with increasing chain length is tested, inhibition of contraluminal PAH influx is first seen with valerate (app.K i 1.4 mmol/l), increasing up to nonanoate (app.K i 0.06 mmol/l) and remaining in this range up to duodecanoate, the last compound of this series which is sufficiently water-soluble. Similarly, the inhibitory potency of aromatic monocarboxylates increases with increasing hydrophobicity. If the fatty acids are esterified, their inhibitory potency is lost. If they are transformed to the respective aldehydes their inhibitory potency is preserved at a reduced degree. Introduction of a hydrophobic methyl-, ethyl-, or propyl-group increases the inhibitory potency. A β-, but not an α-oxo-group augments the inhibitory potency of phenylpropionate analogs, an OH group diminishes it, and a NH2 group abolishes it. Among phenyl-fatty acids an increase in affinity is observed from phenyl- 〈 benzoylamine-〈 phenoxy- 〈 benzoyl-acetate and-propionate. All monocarboxylate compounds, so far tested, do not inhibit contraluminal sulfate and Na+/succinate influx. The data indicate that the PAH transporter interacts with monocarboxylates and also with aldehydes which have a hydrophobic moiety. An additional oxo-group facilitates the interaction. Thus, the benzoyl compounds show the highest affinity observed.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-2013
    Keywords: Nephron ; Sodium Transport ; Calcium Ions ; Antidiuretic Hormone ; Nierentubuli ; Natriumtransport ; Calciumionen ; Antidiuretisches Hormon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An proximalen Tubuli und medullären Sammelrohren von Ratten wurde der isotone Natriumtransport ΆNa iso und die Gleichgewichtskonzentrationsdifferenz Δc Na bei Nettosubstanzfluß und Nettovolumenfluß Null gemessen. Die peritubulären Capillaren waren bei diesen Messungen künstlich durchströmt, und zwar in der ersten Serie mit einer Calcium-freien Lösung bzw. einer Lösung, die 3 mÄq Ca++/l enthielt, in einer zweiten Serie mit einer Lösung, die kein ADH bzw. 5 mE/l ADH enthielt. Zugabe von ADH oder Weglassen von Calcium aus dem Perfusat hatten keinen Einfluß auf den isotonen Natriumtransport. Die Natrium-Gleichgewichtskonzentration bei Nettosubstanzfluß Null war jedoch stark erniedrigt. Die Befunde sprechen dafür, daß bei Fehlen von Calcium oder Zugabe von ADH die Permeabilität für Natriumionen erhöht ist, daß aber im Gegensatz zum Verhalten von Amphibienhäuten der aktive Natriumtransport unbeeinflußt bleibt.
    Notes: Summary Isotonic sodium transport, ΆNa iso, and the transtubular concentration difference, Δc Na, at equilibrium under conditions of zero net solvent and solute fluxes were measured in the proximal tubules and medullary collecting ducts of rats. Peritubular capillaries were simultaneously perfused, in the first group of experiments with a solution containing no Ca++ or 3 mEq/l of Ca++, and in the second group with a solution which contained either no ADH or 5 mU/l of ADH. Addition of ADH or omission of Ca++ from the capillary perfusate did not affect isotonic sodium transport. The equilibrium concentration difference of sodium, Δc Na, was, however, greatly reduced under the same conditions. The results indicate that in the absence of Ca++, or in the presence of ADH, the permeability for sodium is increased, but that in contradistinction to the behaviour of amphibian skins, active sodium transport remains unaffected.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-2013
    Keywords: Perfusion of Peritubular Capillaries ; Water Reabsorption ; Sodium Transport ; Proximal Convolution ; Collecting Duct ; peritubuläre Capillarperfusion ; Wasserresorption ; Natriumtransport ; proximales Konvolut ; Sammelrohre
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An Ratten wurden Mikropunktionsuntersuchungen am proximalen Tubulus und am Sammelrohr bei Durchblutung der peritubulären Capillaren bzw. Vasa recta sowie bei künstlicher Perfusion dieser Blutgefäße durchgeführt. In Abhängigkeit von der Höhe der interstitiellen Natriumkonzentration wurden der Nettonatriumtransport (ΆNa iso) bei gleicher Natriumkonzentration zu beiden Seiten der Tubuluswand und die Gleichgewichtskonzentrationsdifferenz (Δc Na) bei fehlendem Nettovolumen- und Nettosubstanzfluß gemessen. Bei Variation der Natriumkonzentration im Gewebe durch Perfusion der peritubulären Capillaren mit 155 bzw. 300 mÄq/l Na änderten sich weder ΆNa iso noch Δc Na für den proximalen Tubulus (ΆNa iso 8,4 bzw. 7,9·10−5 μÄq · mm−2 · sec−1; Δc Na 24 bzw. 24 mÄq/l). Veränderung der Natriumkonzentration im Blut durch Infusion hypertoner NaCl Lösung oder Peritonealdialyse mit isotoner Mannitlösung führten zu prinzipiell gleichen Ergebnissen. Bei Perfusion der Vasa recta mit Lösungen, die 145 und 300 mÄq/l Natrium entheilten, blieben ΆNa iso wie Δc Na über die Sammelrohrwand ebenfalls konstant (ΆNa iso 4,1 bzw. 4,1·10−5 μÄq · mm−2 · sec−1; Δc Na 98 bzw. 104 mÄq/l). Proximale Tubuli und Sammelrohre verhalten sich demnach bei Variation der interstitiellen Natriumkonzentration gleich. Da die Wasserresorption aus den Sammelrohren von dem durch Gegenstrommultiplikation erzeugten Natriumkonzentrationsanstieg im Markinterstitium abhängt, die Natriumresorption aus den Sammelrohren aber wie die vorliegenden Befunde zeigen von eben dieser Natriumkonzentration unabhängig ist, ist dem Warmblüterorganismus die Möglichkeit gegeben, Natrium- und Wasserresorption unabhängig voneinander zu variieren. Die Natrium- und Wasserresorption aus den Sammelrohren werden jedoch beide durch den Gehalt der Sammelrohrflüssigkeit an permeablen Nichtelektrolyten, wie z. B. Harnstoff, beeinflußt.
    Notes: Summary Micropuncture experiments were performed on proximal tubules and collecting ducts of rat kidneys with and without artificial perfusion of surrounding capillaries or vasa recta respectively. Net sodium flux (ΆNa iso) was estimated under conditions of varying but equal sodium concentrations on both sides of the tubular wall. The transtubular wall equilibrium concentration difference of sodium (Δc Na) was also measured in these nephron segments under conditions of zero volume and solute fluxes. In the proximal tubule ΆNa iso of 8.4 and 7.9×10−5 μeq × mm−2 × sec−1 at sodium concentrations of 155 and 300 meq/l in the perfusion fluid and Δc Na of 24 and 24 meq/l respectively did not vary significantly. Variations of sodium concentrations in blood produced by hypertonic saline infusion or peritoneal dialysis with mannitol resulted in essentially similar values of ΆNa iso and Δc Na. In the collecting ducts also ΆNa iso and Δc Na remained uninfluenced by induced variations in sodium concentrations of the perfusion fluid. ΆNa iso at sodium concentration of 145 and 300 meq/l in the perfusion fluid of vasa recta was 4.1 and 4.1×10−5 μeq × mm−2 × sec−1 respectively and Δc Na was 98 and 104 meq/l respectively. Water reabsorption in the collecting ducts depends on the increase of sodium concentration produced in the medulla by the countercurrent multiplier system. The results represented here indicate that, in mammals sodium reabsorption is independent from the sodium concentration of the interstitial fluid. Therefore the sodium reabsorption and the water reabsorption can be varied independently from each other. Both, sodium and water reabsorption in the collecting ducts are however dependent upon the concentrations of permeable nonelectrolytes such as urea in the collecting duct fluid.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1432-2013
    Keywords: Organic anion transport ; Sulfate transport ; Dicarboxylate transport ; Phenolate transport ; Salicylate transport ; Cinnamate transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to study the specificities of the contraluminal anion transport systems, the inhibitory potency of substituted benzene analogs on influx of [3H]PAH, [14C]succinate, and [35S]sulfate from the interstitium into cortical tubular cells has been determined in situ: (1) Contraluminal [3H]PAH influx is moderately inhibited by benzene-carboxylate and benzene-sulfonate, and strongly by benzene-dicarboxylates,-disulfonates and carboxy-benzene-sulfonates, if the substituents are located at positions 1 and 3 or 1 and 4. The affinity of the PAH transporter to polysubstituted benzoates increases with increasing hydrophobicity, decreasing electron density at the carboxyl group and decreasing pKa. Similar dependencies are observed for phenols. Benzaldehydes which do not carry an ionic negative charge are accepted by the PAH-transporter, if they possess a second partially charged aldehyde or NO2-group. (2) Contraluminal [14C]succinate influx is inhibited by benzene 1,3- or 1,4-dicarboxylates,-disulfonates and 1,3-or 1,4-carboxybenzene-sulfonates. Monosubstituted benzoates do not interact with the dicarboxylate transporter, but NO2-polysubstituted benzoates do. Phenol itself and 2-substituted phenol interact weakly possibly due to oligomer formation. (3) The contraluminal sulfate transporter interacts only with compounds which show a negative group accumulation such as 3,5-dinitro- or 3,5-dichloro-substituted salicylates. The data are consistent with three separate anion transport systems in the contraluminal membrane: The PAH transporter interacts with hydrophobic molecules carrying one or two negative charges (−COO−, −SO 3 − ) or two or more than two partial negative charges (−OH, −CHO, −SO2NH2, −NO2). The dicarboxylate transporter requires two electronegative ionic charges (−COO−, −SO 3 − ) at 5–9 Å distance or one ionic and several partial charges (−Cl, −NO2) at a favourable distance. The sulfate transporter interacts with molecules which have neighbouring electronegative charge accumulation.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1432-2013
    Keywords: N-Methyl-4-phenyl-pyridinium (MPP+) ; N 1-Methylnicotinamide ; Tetraethylammonium (TEA+) ; Choline ; Amiloride ; Cortisol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The efflux of radiolabelled organic cations from the tubular lumen into proximal tubular cells was investigated by using the stop-flow microperfusion method. The efflux rate increased in the sequence: N 1-methylnicotinamide (NMeN+) 〈 cimetidine 〈 tetraethylammonium (TEA+) 〈 N-methyl-4-phenylpyridinium (MPP+). Preloading the animals by i.v. infusion or pre perfusion of the peritubular capillaries with NMeN+ increased the efflux rate of MPP+. Luminal efflux was also augmented when the tubular solution was made alkaline with HCO 3 − or phosphate, whereby HCO 3 − is more effective than phosphate. Replacement of Na+ by Cs+ showed no effect. With i.v. preloading the animals with NMeN+ and with 25 mM HCO 3 − in the luminal perfusate the 2-s efflux follows kinetics with a Michaelis constant K m=0.21 mmol/l and maximal flux J max=0.42 pmol · cm−1 · s−1 and a permeability term with P=37.7 μm2 · s−1. Comparing the apparent luminal inhibitory constant values for MPP+ $$(Ki_{l,MPP^ + } )$$ with the apparent contraluminal $$Ki_{cl,NMeN^ + }$$ values of substrates of homologous series, it was found that (1) limitation by molecular size occurs at the contraluminal cell side earlier than at the luminal cell side; (2) affinity increases with hydrophobicity of the substrates at the luminal cell side, with a steeper or equal slope than at the contraluminal cell side; (3) affinity increases with basicity (i.e. pKa values) at the luminal cell side with a steeper slope than at the contraluminal cell side. Taken together, substrates with low hydrophobicity and low basicity interact at the luminal cell side more weakly than at the contraluminal cell side. On the other hand large, hydrophobic substrates have, at the luminal cell side, a higher affinity than at the contraluminal cell side. Many substrates, however, have equal affinity at the luminal and contraluminal cell sides.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-2013
    Keywords: Proximal Convolution ; Isotonic Reabsorption ; Bicarbonate Buffer ; Lipid Soluble Buffers ; Sodium Transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fluid reabsorption from the proximal convolution of the rat kidney was measured with the Gertz shrinking droplet technique. Simultaneously, the peritubular capillaries were perfused with artificial solutions. In some experimental series, fluid from the shrinking droplet was withdrawn and analysed for Cl−, Na+, and osmolality so that the transtubular transport of Na+, Cl−, and HCO 3 − could be calculated. Capillary perfusate in some experiments was also withdrawn and its pH was measured. The following results were obtained: 1. With increasing concentration of HCO 3 − in the capillary perfusate, the transtubular water, sodium, chloride, and bicarbonate reabsorption increased. 2. The sulfonamide buffers sulfamerazine and glycodiazine (Redul®), which easily penetrate the tubular wall, could, in equimolar concentrations, substitute totally for the bicarbonate buffer in promoting isotonic fluid absorption. 3. Butyrate, propionate, and acetate were also effective; pyruvate, lactate, and paraaminohippurate, however, were not. 4. The effect of HCO 3 − and glycodiazine on isotonic absorption was shown to depend exclusively on the concentration of the buffer anion and not on the concentration of undissociated acid or pH. From these data it is suggested that for proximal isotonic absorption of water, sodium, and chloride, the reabsorption of buffer anions via H+ secretion and nonionic diffusion may be essential. The H+ secretion or the buffer anion absorption across the luminal cell wall may secondarily influence the active Na+ transporting mechanism located at the basal cell site either by a luminal H+−Na+ exchange mechanism or by a lyotropic effect which would increase the Na+ permeability of the luminal cell site. Thereby more Na+ would be delivered to the Na+ pumping site and the rate of Na+ pumping would be augmented.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...