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  • 1975-1979  (4)
  • Kidney  (2)
  • Sodium channel  (2)
  • Permeability
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 300 (1977), S. 57-66 
    ISSN: 1432-1912
    Keywords: Aminoglycoside ; Gentamicin ; Kidney ; Electron microscopic autoradiography ; Lysosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Upon intravenous injection of 3H-gentamicin in rats, radioactivity in serum rapidly declined to 3% of total within 1 h. Kidneys accumulated a constant amount (14%) of the injected radioactivity between 2 and 6 h after injection. In mice, simultaneous or prior application of unlabeled gentamicin (10 mg/kg) diminished the renal concentration of 3H-gentamicin, and aprotinin (10 mg/kg) was able to compete with labeled aprotinin. Aprotinin did not diminish the renal accumulation of gentamicin and vice versa. However, since 10 mg/kg aprotinin raised also the plasma concentrations of both 3H-gentamicin and 125I-aprotinin, the evidences resulting from these experiments are limited. Mouse kidney cortex was processed for light and electron microscopic autoradiography at different times following i.v. injection of 3H-gentamicin. Gentamicin enters the apical part of proximal tubule cells. Initially, brush border and basement membrane labeling is prominent, whereas lysosomes appear as intense and prevalent stores 20 min or later after injection. Fractionation of 3H-gentamicin loaded kidneys showed a similar distribution pattern of radioactivity and the lysosomal marker β-galactosidase. The same was true when the crude lysosomal fraction was subjected to density gradient centrifugation, which corroborates the microscopical findings. Radioactivity is partially bound to lysosomal structures, for repeated freezing of loaded lysosomes left 35% of radioactivity particle-bound. It is concluded that both gentamicin and peptides are handled in a similar manner by adsorption, followed by endocytosis and lysosomal sequestration in proximal tubule cells.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Sodium channel ; Calcium ; Cyclic GMP ; Cerebellum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sea anemone toxin II (ATX II) and MCD-peptide, like other depolarizing agents, raise the content of cGMP and to a lesser extent of cAMP in mouse cerebellar slices. Na+ influx and Ca2+ movement are involved in their mode of action, as indicated by the following observations: 1. The rise of cGMP due to ATX II, MCD-peptide and high potassium was diminished when Na+ had been replaced by Li+. 2. The effects of both toxins and veratridine, but not of high potassium stimulation were prevented by tetrodotoxin (TTX). 3. The cGMP accumulation due to both toxins was abolished in the absence of extracellular Ca2+. 4. The so-called Ca2+-antagonist (−)-D-600 blocked the increase of cGMP due to ATX II, MCD-peptide, veratridine and high potassium. 5. ATX II stimulated the 45Ca2+ uptake in mouse cerebellar slices which was prevented by TTX and (−)-D-600.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 300 (1977), S. 67-76 
    ISSN: 1432-1912
    Keywords: Polycations ; Aminoglycosides ; Kidney ; Brush border membrane ; Lysosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Experiments with Brush Border Membranes Drugs were screened for inhibition of 125I-aprotinin binding to isolated rat renal brush border membranes. Cationic polymers were effective, and their primary amino groups were crucial. The polycationic aminoglycosides displaced 125I-aprotinin with low concentrations (50% inhibition by 50 μg/ml of gentamicin). The decreasing sequence of both number of amino groups and of inhibitory potency was: neomycin 〉 tobramycin 〉 gentamicin 〉 kanamycin 〉 streptomycin. Binding of 3H-gentamicin-C1 to the brush border membrane was saturable. The Scatchard plot indicated an association constant of 43 mM−1, and 18 nmoles per mg of membrane protein for the number of binding sites. Inhibition of 125I-aprotinin binding by gentamicin was competitive. The inhibition constant (KI) was 20 μg/ml with concentrations of 8 and 40 μg/ml of gentamicin. 2. Experiments with Lysosomes Gentamicin and aprotinin (200 μg/ml) activated β-glucuronidase and β-galactosidase from renal lysosomes, but not acid phosphatase. Gentamicin and aprotinin (300 μg/ml) increased the release of acid phosphatase from intact renal lysosomes. Lysosomal degradation of 125I-aprotinin into acid soluble split products was much slower than that of 125I-insulin. From our present and previous results it is concluded that binding to the brush border membrane occurs with chemically quite different, however basic drugs and that the number of amino groups per molecule is relevant. Nephrotoxicity of aminoglycosides may be related to their endocytic uptake through a direct action on lysosomes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1912
    Keywords: Cyclic nucleotides ; Neurotoxins ; Sodium channel ; Neural tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary cAMP and cGMP were measured in mouse cerebellar slices, neural cell lines and primary nerve cell cultures from rats after treatment with different neurotoxins and high potassium. 1. Sea anemone toxin II (ATX II), which is known to keep the activated sodium channels open, raised the cGMP content of mouse cerebellar slices up to 35-fold and doubled their cAMP content. Mast-cell-degranulating peptide (MCD-peptide) from been venom increased cGMP levels up to 15-fold. The effects of both toxins on the cyclic nucleotide content were mimicked by depolarizing agents, like high potassium and veratridine. Primary nerve cell cultures (4 weeks old) responded to ATX II and high potassium with an increase of both cGMP and cAMP, however to a smaller extent as compared with slices. Excitable structures appear to be relevant, because younger cultures (2 weeks and less) and several neural cell lines did not respond to ATX II. 2. Specific neurotoxins like tetanus toxin, botulinum A toxin and apamin from bee venom had no effect on the cyclic nucleotide content of cerebellar slices and of primary nerve cell cultures. In cerebellar slices the potassium-stimulated increase of cAMP and cGMP was not affected by previous exposure of the slices to tetanus toxin or apamin. We conclude that opening of sodium channels in excitable membranes generally raises the cyclic nucleotide content whereas the mode of action of specific neurotoxins is not reflected by changes in the overall content of cyclic nucleotides.
    Type of Medium: Electronic Resource
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