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  • Tetanus toxin  (14)
  • Acetylcholine  (3)
  • Kidney  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 242 (1989), S. 245-248 
    ISSN: 0014-5793
    Keywords: (Chromaffin cell) ; Exocytosis ; Light chain ; Streptolysin O ; Tetanus toxin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0014-5793
    Keywords: E. coli, Chromaffin cell ; Exocytosis ; Recombinant protein ; Site directed mutagenesis ; Tetanus toxin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0014-5793
    Keywords: (Aplysia) ; Central synapse ; Heavy chain ; Light chain ; Tetanus toxin ; Transmitter release
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 312 (1980), S. 255-263 
    ISSN: 1432-1912
    Keywords: Acetylcholine ; Tetanus toxin ; Botulinum toxin ; Myenteric plexus ; Transmitter release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of tetanus and botulinum A toxin were studied on the electrically stimulated myenteric plexus-ileum strip of the guinea pig. The concentrations used were in the range of 104–106 mouse LD50/ml. 1. Tetanus and botulinu, A toxin slowly decrease the amplitude of the contractile response to field stimulation in a dose-dependent manner without influencing the sensitivity to acetylcholine of the smooth muscle. 2. Development of paralysis is preceded by a latent period. Washing and antitoxin slow the paralytic process only when applied during the latent period. 3. The time course of development of paralysis depends on the activity of the strip. It can be slowed by rest, high [Mg2+], or low [Ca2+], and accelerated by raising the stimulation frequency. 4. Substances like 4-aminopyridine, sea anemone toxin II and scorpion toxin which prolong the membrane depolarization restore temporarily the contraction of partially paralysed muscle strips. 5. Poisoned preparations do not differ from controls in their total acetylcholine contents, whereas formation as well as release of [3H]-acetylcholine are decreased by either toxin. It is concluded that a) tetanus toxin and botulinum A toxin are qualitatively indistinguishable with respect to their actions on the postganglionic cholinergic neurons in the ileum, botulinum A toxin being 5 times more potent than tetanus toxin, b) the effects of the toxins at postganglionic cholinergic neurons in the ileum and at motor nerve endings are qualitatively similar, botulinum A toxin being about 500 times more potent than tetanus toxin at the latter preparation (see Habermann et al., 1980b, c) both toxins influence the turnover of acetylcholine but not its tissue concentration.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 316 (1981), S. 135-142 
    ISSN: 1432-1912
    Keywords: Tetanus toxin ; Botulinum A toxin ; Choline ; Gangliosides ; Fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tetanus toxin and, to a lesser degree, botulinum A toxin inhibit partially and noncompetitively the uptake of [3H]choline into a crude synaptosomal fraction from rat brain cortex. Botulinum toxin acts by its neurotoxin content. The effect is not due to nonspecific synaptosomal damage by the toxins as shown by the lactate dehydrogenase occlusion test, by the absence of swelling and by the preservation of choline stores. The ratio between [3H]acetylcholine and [3H]choline was decreased by both toxins. Inhibition by either toxin depends strongly on the temperature and duration of incubation, and is preceded by an initial latency period. The effect of tetanus toxin, once manifest, is largely resistant against antitoxin. It is not significantly diminished by pretreatment of the synaptosomes with V. cholerae neuraminidase. Fixation of 125I-tetanus toxin proceeds fast, is largely independent of temperature and is diminished by pretreatment of the synaptosomes with neuraminidase. Thus only some of the fixation sites, and not the long-chain gangliosides, are required for the effects of tetanus toxin. A slow, temperature-sensitive process links the fixation with the action. In contrast to rat synaptosomes the chicken preparation is more sensitive to botulinum A than to tetanus toxin, which reflects the differences in sensitivity between live birds and rodents. Our data underline the similarities between the effects of tetanus and those of botulinum A toxin. Their dependence on time and temperature, the time dependence of efficacy of antitoxin, and the concordance in species specificity indicate that the in vitro system mirros some crucial features of poisoning of isolated organs and live animals.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 316 (1981), S. 143-148 
    ISSN: 1432-1912
    Keywords: Tetanus toxin ; Botulinum toxin ; Acetylcholine ; Calcium ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Slices or particles from rat forebrain cortex were preloaded with [3H]choline, and the release of [3H]acetylcholine was evoked with potassium ions in a superfusion system. Release depended on the presence of calcium. 1. Incubation of the preloaded tissue preparation for 2 h with tetanus or botulinum A toxin did not change the [3H]acetylcholine content or the ratio [3H]acetylcholine/[3H]choline. Tetanus toxin diminished, dependent on dose and time, the release of [3H]acetylcholine evoked by 25 mM K+. It was about ten times more potent than botulinum A toxin. The effect of botulinum toxin was due to its neurotoxin content. Raising the potassium concentration partially overcame the inhibition by the toxins. Hemicholinium-3, applied to preloaded slices, left the subsequent [3H]acetylcholine release unchanged. Pretreatment of particles with neuraminidase diminished the content of long-chain gangliosides to the detection limit. Such particles remained fully sensitive to tetanus toxin, and at least partially sensitive to botulinum A toxin. 2. The potassium or sea anemone toxin II stimulated uptake of 45Ca2+ into cortex synaptosomes or particles was not inhibited by either toxin. Both toxins appear to impede the Ca2+-dependent mobilization of an easily releasable acetylcholine pool, without inhibiting the transmembranal calcium fluxes.
    Type of Medium: Electronic Resource
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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 133-138 
    ISSN: 1432-1912
    Keywords: Tetanus ; Botulism ; Acetylcholine ; Nerve tissue ; Cell cultures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Primary nerve cell cultures derived from embryonic rat central nervous system form [3H]ACh from exogenous [3H]Ch, and release it upon potassium depolarization. Pretreatment of the cultures with botulinum-A toxin or tetanus toxin diminishes the cellular accumulation of [3H]ACh. Poisoning the cultures during the period of [3H]Ch uptake fails to lower [3H]ACh formation. Dependent on dosage, both toxins suppress the release of [3H]ACh upon potassium depolarization. Heat-denaturated toxins as well as tetanus toxin preincubated with tetanus antitoxin were without effect.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1912
    Keywords: Tetanus toxin ; Botulinum A toxin ; Neurotransmitter ; Uptake ; Release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of tetanus toxin and botulinum A toxin on the uptake and evoked release of various neurotransmitters were studied using particles from rat forebrain, corpus striatum and spinal cord. 1. Uptake. Tetanus toxin partially inhibits the uptake of glycine and choline into spinal cord synaptosomes. The effect on glycine uptake becomes statistically significant after a lag period of 60\2-120 min. It is no longer present when the toxin is heated, antitoxin-treated or toxoided. The inhibition by botulinum A toxin of choline uptake into spinal cord synaptosomes is weak but measurable, that of glycine uptake is at the borderline of detection. The uptake of GABA into forebrain cortex synaptosomes is slightly inhibited by tetanus toxin but hardly by botulinum A toxin. The effects of tetanus toxin and botulinum A toxin on the uptake of noradrenaline into striatal synaptosomes are negligible. 2. Release. Tetanus toxin inhibits the potassium (25 mM) evoked release of radioactivity from rat forebrain cortex particles preloaded with labelled neurotransmitters. The sensitivity decreases in the following order: Glycine 〉 GABA \2〉 acetylcholine. The toxin also inhibits the release of radioactivity from striatal particles preloaded with labelled noradrenaline. It is always 10\2-50 times more potent on spinal cord than on brain particles. The sensitivity of the evoked release from the spinal cord decreases in the order glycine 〉 GABA 〉 acetylcholine 〉 noradrenaline. The toxin is identical with the causative agent because toxin-antitoxin complexes, toxoid and heated toxin do not influence the release from particles preloaded with glycine (spinal cord), GABA (forebrain) and noradrenaline (striatum). Botulinum toxin resembles tetanus toxin by its ability to diminish the release of radioactivity from preloaded forebrain (acetylcholine 〉 GABA), striatal (noradrenaline), or spinal cord (glycine) particles. The botulinum toxin effect on the striatum (noradrenaline) and on the spinal cord (glycine) is due to its neurotoxin content. The identity of the toxin and the causative agent has been established by preheating and preincubation with antitoxin. It is proposed that a) tetanus and, however to a much lesser degree, botulinum A toxin act in a basically similar manner on a process underlying the function of synapses in general, and b) the pronounced sensitivity of glycine and GABA release from spinal cord, together with the axonal ascent of tetanus toxin, may be crucial in the pathogenesis of tetanus.
    Type of Medium: Electronic Resource
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