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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 50 (1988), S. 111-122 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Urological research 7 (1979), S. 143-148 
    ISSN: 1434-0879
    Keywords: Urate ; Oxalate ; Renal Handling ; Precipitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Both urate and oxalate are organic acids of considerable clinical interest, owing to their limited solubility. Calcium oxalate is the most frequent constituent of renal calculi and occasionally precipitates in body fluids. Urate precipitations are common in the kidney and in various other tissues. In this paper, a short outline of the present knowledge of renal handling of these substances will be followed by some conclusions as to the possible relevance of this knowledge for the understanding of urolithiasis and intrarenal precipitation. Direct (micropuncture) data are available for urate in the rat (1,6, 7, 10, 21, 23, 28, 36, 42), rabbit (35), dog (34) and cebus monkey (33) and in the rat only for oxalate (11, 15, 20).
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 403 (1985), S. 446-448 
    ISSN: 1432-2013
    Keywords: Cl−-secretion ; Cl−-channel ; K+-channel ; CAMP mediated secretion ; patch clamp method ; rectal gland of shark
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isolated rectal gland tubules (n≈1000) of dogfish (Squalus Acanthias) were perfused in vitro. Individual channels in the apical and basolateral cell membrane were recorded with the patch clamp method. K+-channels were present in excised membrane patches of the basolateral membrane in stimulated (dbcAMP + forskolin + adenosine) and in nonstimulated state. Cl−-channels were found only in patches of the apical cell membrane when the tubule was stimulated. Cell attached recordings and simultaneous transepithelial PD measurements were obtained while the segment was stimulated. It is shown that concomitant with the increase in lumen negative PD “silent” membrane patches of the apical cell membrane suddenly develop Cl−-channel activity. It is concluded that stimulation of rectal gland tubules “activates” Cl−-channels in the apical cell membrane.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: Proximal tubule ; Kidney ; K+ conductance ; Cell membrane potential ; Ouabain temperature ; Phlorizin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In isolated perfused segments of the mouse proximal tubule, the potential difference across the basolateral cell membrane (PDbl) was determined with conventional microelectrodes. Under control conditions with symmetrical solutions it amounted to −62±1 mV (n=118). The potential difference across the epithelium (PDte) was −1.7±0.1 mV (n=45). Transepithelial resistance amounted to 1.82±0.09 kΩ cm (n=28), corresponding to 11.4±0.6 Ω cm2. Increasing bath potassium concentration from 5 to 20 mmol/l depolarized PDbl by +24±1 mV (n=103), and PDte by +1.6±0.1 mV (n=19). Thus, the basolateral cell membrane is preferably conductive to potassium. Rapid cooling of the bath perfusate from 38°C to 10°C led to a transient hyperpolarization of PDbl from −60±1 to −65±1 mV (n=21) within 40 s followed by gradual depolarization by +18±1% (n=14) within 5 min. The transepithelial resistance increased significantly from 1.78±0.11 kΩ cm to 2.20±0.21 kΩ cm (n=15). Rapid rewarming of the bath to 38°C caused a depolarization from −61±2 mV (n=17) to −43±2 mV (n=16) within 15 s followed by a repolarization to −59±2 mV (n=10) within 40 s. Ouabain invariably depolarized PDbl. During both, sustained cooling or application of ouabain, the sensitivity of PDbl to bath potassium concentration decreased in parallel to PDbl pointing to a gradual decrease of potassium conductance. Phlorizin hyperpolarized the cell membrane from −59±2 to −66±1 mV (n=13), virtually abolished the transient hyperpolarization under cooling, and significantly reduced the depolarization after rewarming from +17±2 mV (n=16) to +9±3 mV (n=9). The present data indicate that the contribution of peritubular potassium conductance to the cell membrane conductance decreases following inhibition of basolateral (Na++K+)-ATPase. Apparently, cooling from 37° to 10°C does not only reduce (Na−+K+)-ATPase activity but in addition luminal sodium uptake mechanisms such as the sodium glucose cotransporter. As a result, cooling leads to an initial hyperpolarization of the cell followed by depolarization only after some delay.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2013
    Keywords: Torasemide ; Cortical thick ascending limb of the loop of Henle ; Rabbit ; Na+2Cl−K+ cotransporter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to examine compounds related to torasemide with respect to their ability to block the equivalent short circuit current, corresponding to the rate of chloride reabsorption, in isolated in vitro perfused cortical thick ascending limbs of Henle of the rabbit. The torasemide molecule was modified with respect to the anionic sulfonylurea group, and the secondary amine linked to the pyridine ring. Our results indicate that only few of the tested 48 torasemide-related compounds were able to inhibit from both epithelial sides like torasemide. Only few of the tested compounds were equally effective as torasemide from the lumen side. Some analogues were acting only from the luminal side and some only from the peritubular side. The correlations between structure and potency of inhibition from the luminal side allow the following conclusions: a) The secondary amine moiety linked to the pyridine ring (toluidine in case of torasemide) can be replaced by a cycloalkylamine or, with some loss of inhibitory potency, by alkylamines. The inhibitory potency is increased with the number of C-atoms in the cycloalkylamine substituted compounds (optimum C7 to C8), and is also depending on the length of the alkylamines (optimum C4). b) The secondary amine seems to be required since nitrogen cannot be replaced by −S- or −SO2-. c) The sulfonylurea group cannot be substituted by other anionic groups such as −SO 3 − or −COO−. d) If the pyridine ring is replaced by a NO2-substituted phenyl ring, the inhibitory potency from the luminal side is lost. However, these compounds act still (with some loss of potency) from the peritubular side. The data indicate that several of the conclusions drawn from our previous systematic surveys of chloride channel blockers and loop diuretics of the furosemide type, i.e. blockers of the Na+2Cl−K+ carrier, hold also true for compounds related to torasemide. In addition, the pyridine ring is responsible for some specific structure activity correlations.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2013
    Keywords: Human sweat duct ; Cl− conductance ; Cl− channel blockers ; Cystic fibrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To characterize the chloride conductance of human sweat duct the effect of various analogues of diphenylamine-2-carboxylate was investigated on the transepithelial potential difference (PDT) and resistance (R T ) of isolated microperfused sweat ducts. Although the most powerful analogues which block Cl− channels in various secretory and absorptive epithelia were ineffective, a number of analogues (in particular Cl substituted ones) were found which at high concentrations significantly and reversibly increased PDT andR T . The data suggest that the main chloride conductance pathway of sweat duct epithelium resides in the cell membranes rather than in the tight junctions. In addition the different blocking spectra of the chloride conductances of sweat duct and tracheal epithelium (Welsh MJ, Science 232:1648, 1986) suggest that the combined impairment of both conductances in cystic fibrosis does not result from a molecular defect in the Cl− channels.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2013
    Keywords: ADH ; Transepithelial ion net fluxes ; Na+, Cl−, K+, Ca2+ and Mg2+ transport ; Electron microprobe ; Mouse kidney ; Cortical and medullary thick ascending limb of Henle's loop ; In vitro microperfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of antidiuretic hormone (arginine vasopressin, AVP) on transepithelial Na+, Cl−, K+, Ca2+ and Mg2+ net transports was investigated in medullary (mTAL) and cortical (cTAL) segments of the thick ascending limb (TAL) of mouse nephron, perfused in vitro. Transepithelial net fluxes (J Na +,J Cl −,J K +,J Ca 2+,J Mg 2+) were determined by electron probe analysis of the collected tubular fluid. Transepithelial potential difference (PDte) and transepithelial resistance (Rte) were measured simultaneously. cTAL segments were bathed and perfused with isoosmolal, HCO 3 − containing Ringer solutions, mTAL segments were bathed and perfused with isoosmolal HCO 3 − free Ringer solutions. In cTAL segments, AVP (10−10 mol·l−1) significantly increasedJ Mg 2+ andJ Ca 2+ from 0.39±0.08 to 0.58±0.10 and from 0.86±0.13 to 1.19±0.15 pmol·min−1 mm−1 respectively. NeitherJ Na + norJ Cl −, (J Na +: 213±30 versus 221±28 pmol·min−1 mm−1,J Cl −: 206±30 versus 220±23 pmol·min−1 mm−1) nor PDte (13.4±1.3 mV versus 14.1±1.9 mV) or Rte (24.6±6.5Ω cm2 versus 22.6±6.4Ω cm2) were significantly changed by AVP. No significant effect of AVP on net K+ transport was observed. In mTAL segments, Mg2+ and Ca2+ net transports were close to zero and AVP (10−10 mol·l−1) elicited no effect. However NaCl net reabsorption was significantly stimulated by the hormone,J Na + increased from 107±33 to 148±30 andJ Cl − from 121±33 to 165±32 pmol·min−1 mm−1. The rise inJ NaCl was accompanied by an increase in PDte from 9.0±0.7 to 13.5±0.9 mV and a decrease in Rte from 14.4±2.0 to 11.2±1.7 Ω cm2. No K+ net transport was detected, either under control conditions or in the presence of AVP. To test for a possible effect of HCO 3 − on transepithelial ion fluxes, mTAL segments were bathed and perfused with HCO 3 − containing Ringer solutions. With the exception ofJ Ca 2+ which was significantly different from zero (J Ca 2+: 0.26±0.06 pmol·min−1 mm−1), net transepithelial fluxes of Na+, Cl−, K+ and Mg2+ were unaffected by HCO 3 − . In the presence of AVP,J Mg 2+ andJ Ca 2+ were unaltered whereasJ NaCl was stimulated to the same extent as observed in the absence of HCO 3 − . In conclusion our results indicate heterogeneity of response to AVP in cortical and medullary segments of the TAL segment, since AVP stimulates Ca2+ and Mg2+ reabsorption in the cortical part and Na+ and Cl− reabsorption in the medullary part of this nephron segment.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2013
    Keywords: Isolated perfused tubule ; Macula densa ; Intracellular voltage ; Furosemide ; Tubuloglomerular feedback
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The macula densa cells of the juxtaglomerular apparatus probably serve as the sensor cells for the signal which leads to the appropriate tubuloglomerular feedback response. The present study reports basolateral membrane voltage (PDbl) measurements in macula densa cells. We isolated and perfused in vitro thick ascending limb segments with the glomerulus, and therefore the macula densa cells, and the early distal tubule still attached. Macula densa cells were impaled with microelectrodes under visual control. PDbl was recorded in order to examine how these cells sense changes in luminal NaCl concentrations. The addition of furosemide, a specific inhibitor of the Na+2Cl−K+ cotransporter in the thick ascending limb, to the lumen of the perfused thick ascending limb hyperpolarized PDbl from −55±5 mV to −79±4 mV (n=7). Reduction of NaCl in the lumen perfusate from 150 mmol/l to 30 mmol/l also hyperpolarized PDbl from −48±3 mV to −66±5 mV (n=4). A Cl− concentration step in the bath from 150 mmol/l to 30 mmol/l resulted in a 24±4 mV (n=4) depolarization of PDbl. This depolarization of PDbl was absent when furosemide was present during the Cl− concentration step. These data suggest that the macula densa cells sense changes in luminal NaCl concentration via coupled uptake of Na+ and Cl−. The transport pathways for NaCl transport in macula densa cells are probably identical to those in the thick ascending limb: the (Na++K+)-ATPase in the basolateral membrane drives Na+ and Cl− uptake via the luminal Na+2Cl−K+ cotransport, Cl− leaves the cell via basolateral Cl− channels and K+ recycles across the apical membrane via K+ channels. Changes in intracellular Cl− activity as a result of altered luminal NaCl uptake, and thus voltage changes of the basolateral membrane are probably the first signal in the tubuloglomerular feedback regulation.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 357 (1975), S. 201-207 
    ISSN: 1432-2013
    Keywords: Allantoin ; Uricase ; Kidney ; Clearance ; Micropuncture ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Renal excretion of allantoin was measured by tracer techniques. After injection of 2-C14 urate and H3 inulin, clearances of allantoin and inulin were measured and both proximal and distal tubules were micropunctured. In confirmation of earlier results 2-C14 urate injected into an intact animal is very rapidly converted to C14 allantoin: after 15 min more than 90% of urinary tracer is present as allantoin. It was further observed that 1) allantoin clearance is essentially identical with inulin clearance over a wide range of urine flows; 2) no net transport of allantoin occurs in either proximal or distal tubules. Clearly allantoin is handled by the rat kidney like inulin. The total excretion of filtered allantoin unlike that of filtered urate provides an easy and effective mechanism for animals possessing the enzyme uricase to dispose of their purine loads.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 374 (1978), S. 243-248 
    ISSN: 1432-2013
    Keywords: Oxalate ; Wistar rat ; Microperfusion ; Microinfusion ; Organic acid secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal transport of14C-oxalate was studied in the rat by clearance and micropuncture techniques. The ultrafilterability of oxalate was 0.98±0.02 (n=7). Fractional clearance of oxalate was significantly above unity in antidiuresis and volume expansion: mean 1.24 ±0.04 (n=115). Pyrazinamide (1.1·10−3 mol/kg BW) and probenecid (0.35·10−3 mol/kg BW) had no significant effect on oxalate clearance. P-aminohippurate (1.45·10−3 mol/kg BW) and urate (0.48 ·10−3 mol/kg BW) depressed the fractional clearance of oxalate significantly from 116 to 91 and from 125 to 90%, respectively. Excess excretion of14C-oxalate over3H-inulin was invariably demonstrable in peritubular microperfusion experiments (n=5) and in microinfusions underneath the kidney capsule (n=4). Together with the first 50% of3H-inulin 58±2% of the total14C-oxalate were excreted in the peritubular microperfusions, and 64±3% in the subcapsular microinfusions. In tubular microinfusion experiments (n=36) urinary14C-oxalate recovery was almost complete after early proximal microinfusion (93±4%) and complete after late proximal microinfusion (102±4%). In continuous microperfusion experiments of proximal tubules (n=42) a small but highly significant outflux of14C-oxalate of 7% per mm perfusion distance was found. The data suggest that oxalate is freely filterable at the glomerular site. A small but significant amount of oxalate is reabsorbed in the proximal nephron. Most likely at the same site and in the pars recta oxalate is secreted and tubular load increased to 124% of filtered load. This amount is excreted in final urine. The secretion of oxalate is inhibited by organic acids which are known to be secreted by the proximal tubule and the pars recta.
    Type of Medium: Electronic Resource
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