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  • Palytoxin  (7)
  • Tetanus Toxin  (7)
  • Depolarization  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 861 (1986), S. 165-176 
    ISSN: 0005-2736
    Keywords: (Erythrocyte membrane) ; (Na^+ + K^+)-ATPase ; Ligand binding ; Membrane permeability ; Ouabain ; Palytoxin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 649 (1981), S. 481-486 
    ISSN: 0005-2736
    Keywords: (Erythrocyte) ; Hemolysis ; K^+loss ; Palytoxin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 688 (1982), S. 486-494 
    ISSN: 0005-2736
    Keywords: (Erythrocyte) ; Amphotericin B ; Palytoxin ; Permeability
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 1-9 
    ISSN: 1432-1912
    Keywords: Depolarization ; Ion channels ; Phosphatidylinositol ; Inositol phosphates ; Voltage-dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the accumulation of inositol phosphates (InsP) due to depolarization. A particulate preparation of rat brain was introduced to rule out transmitter activated mechanisms and to allow free access for drugs of high molecular weights. Potassium depolarization doubled InsP within a few minutes. InsP accumulation depended on time and K+ concentration, and was affected neither by tetrodotoxin nor by atropine. Radioactive metabolites co-eluted with inositol mono-phosphate and inositol bis-phosphate, whereas only minor amounts appeared with inositol tris-phosphate. The content in phosphatidylinositols was decreased. No evidence was found for the involvement of a neurotransmitter. Sea anemone toxin II (around 1 μmol/l), which keeps the Na+-channels open, promoted the InsP accumulation in an atropine-resistant manner. Tetrodotoxin prevented it when given before, and inhibited it when given after initiation by sea anemone toxin II. Moreover the K+ channel blockers 4-aminopyridine, dendrotoxin and tetraethylammonium all caused InsP accumulation. Palytoxin was by far the most potent promoter of InsP accumulation with a detection limit below 10 pmol/l, and displayed a unique bell-shaped concentration-effect correlation. Ouabain (3 μmol/l) and above) also elicited the InsP accumulation. The response to carbachol was not only inhibited completely by atropine, but also partially (more than 50%) by tetrodotoxin, which indicates the involvement of voltage-dependent sodium channels in the receptor-triggered InsP accumulation. Thus independent of the causative agent, depolarization promotes an InsP accumulation. We conclude that degradation of phosphatidylinositols is mediated not only by receptor occupation but also by a positive shift in membrane voltage.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 327-340 
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Pharmacokinetics ; Central Nervous System ; Iodine Labelling ; Receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to understand the symptomatology of generalized tetanus from the pharmacokinetics of the toxin, 125I-labelled toxin was injected i.v. in rats without and with antitoxin. 1. After a few hours latency, brain stem and spinal cord concentrate radioactive material up to the third day. The decline of radioactivity is very slow, semilogarithmic, and can be followed up to the 24th day after injection. In contrast, forebrain and cerebellum do not bind measurable radioactivity. Less than 1% of the radioactivity injected is found in the CNS. 2. The symptoms of tetanus start some time after the bulk of labelled toxin has been taken up by the CNS. They cease before all radioactivity has left it. 3. Antitoxin, given simultaneously, prevents the onset of symptoms and the uptake of radioactivity by the CNS. When given 10 h after labelled toxin, it nearly abolishes the fixation and still prevents the onset of symptoms. When given 48 h after toxin, it is nearly ineffective in both respects. Antitoxin first delays, then enhances the elimination of labelled toxin from the blood. 4. Labelled antitoxin is not enriched in the CNS. 5. The uptake of radioactivity into various parts of spinal cord corresponds well to their relative content in grey matter. 6. The pharmacokinetic behaviour of 125I-toxoid resembles that of toxin. However, in order to get measurable fixation to the CNS at least 50 times higher amounts are to be applied. It is concluded that the barrier between blood and CNS is practically impermeable to tetanus toxin. The results can be harmonized best with the assumption that generalized tetanus is nothing else than a multiple local tetanus.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 177-182 
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Iodine Labeling ; Spinal Cord ; Histoautoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 125I-labeled tetanus toxin was injected intravenously and intramuscularly in rats. Specific localisation within the spinal cord was obtained by histoautoradiography. 1. In generalized tetanus grain density was maximal in the ventral grey matter of spinal cord. The grains were closely correlated to the motoneurons and their neuropil. Other areas showed background activity only. 2. In local tetanus the injected side was labeled selectively. High grain density regularly covered a distinct group of motoneurons and their neuropil. 3. There is some evidence for intracellular accumulation of the toxin since the maximum of grain density was found over the perikarya whilst the nucleus corresponded to a minimum. 4. Cells yielding high grain density were less intensively stained with toluidine blue than neighbouring unlabeled cells. It is concluded from these experiments that tetanus toxin develops its action within or around selected motoneurons and that it induces morphological alterations there.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 75-88 
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Tetanus Antitoxin ; Local Tetanus ; Spinal Cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 0 1. Local tetanus was produced in rats by application of sublethal doses of 125I-tetanus toxin into the right m. gastrocnemius. Radioactivity was found in the lumbar part of the spinal cord for at least 24 days which is indicative of a long-lasting binding of toxin to its target organ. Radioactivity appears in the lumbar region before local tetanus becomes manifest. 2. The influence of antitoxin on both local tetanus and radioactivity of the lumbar cord heavily depends on the time of its application. When it is injected simultaneously into a foreleg, it prevents the symptoms and the spinal concentration process. When given ten hours after toxin, it does not change appreciably the severity of local tetanus; it diminishes, however, the radioactivity accumulating in the spinal cord. Antitoxin, given 48 hours after toxin, is ineffective in both respects. 3. 22 hours after application, about 9% of the initial radioactivity still persists in the injected leg; 50 hours after application, only 1–2% are still present. 4. Plasma radioactivity is measurable for between 50 and 96 hours in animals given 125I-toxin i.m. It is higher in animals having received antitoxin 10 hours after the toxin or simultaneously with toxin. 5. Labelled toxoid was prepared by formol treatment of labelled toxin. Following i.m. injection, toxoid was bound to a lesser degree and for a shorter time by the lumbar cord than was toxin. Like toxin, toxoid was found in the ipsilateral sciatic nerve, and simultaneous application of antitoxin prevented its appearance there as wells as in the lumbar cord. As with toxin, plasma radioactivity after injection of labelled toxoid was increased by simultaneous application of antitoxin into another leg. 6. It is concluded that antitoxin prevents the entrance of toxin into the spinal cord, but does neither remove nor detoxify appreciable amounts of radioactive material once fixed.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 97-106 
    ISSN: 1432-1912
    Keywords: Tetanus Toxin ; Botulinum A Toxin ; Synaptosomes ; Neuraminic Acid ; Fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Rat brain homogenate and synaptosomes from rat brain bind botulinum toxin. The binding is accompanied by partial inactivation. The binding decreases with increasing ionic strength. A considerable fixation of tetanus toxin can still be demonstrated under conditions which prevent the fixation of botulinum toxin. 2. Only the grey substance, not the white substance from bovine brain is able to bind the toxin. 3. Upon pretreatment with neuraminidase, synaptosomes lose nearly all of their binding capacity. However, neither gangliosides nor ganglioside-cerebroside mixtures nor brain extracts could replace the synaptosomes. Thus botulinum A toxin closely resembles tetanus toxin in its ability to react with (a) neuraminidase-sensitive site(s) of the grey matter of the CNS. It differs from tetanus toxin by its stronger sensitivity against ionic forces and by its failure to react with certain gangliosides.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 323 (1983), S. 269-275 
    ISSN: 1432-1912
    Keywords: Palytoxin ; Tetraphenylphosphonium ; Depolarization ; Binding ; Borate ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Palytoxin in concentrations as low as 10−11 to 10−12 M promotes the outflow of the lipophilic [3H]-tetraphenylphosphonium ion from particulate brain cortex of guinea-pigs and rats, and from preloaded crude synaptosomes of rats, which indicates depolarization. The outflow is not influenced by tetrodotoxin or the calcium channel blocker nimodipin, or by substitution of choline for Na+ ions. It is increased by Ca2+ and by borate, the latter interacting with the toxin itself. To assess the fixation of palytoxin to biological membranes, a binding step was installed before the depolarization step. Palytoxin binds to membranes from rat brain, liver, kidney, human and dog erythrocytes, and to a lesser degree to liposomes made from rat brain or erythrocyte lipids. Binding is reversible. It is decreased by mild physical pretreatments of crude synaptosomes. Palytoxin binding is increased in the presence of micromolar concentrations of Ca2+ or borate. It is concluded that the potentiation of palytoxin actions by Ca2+ or borate is at least partially due to the promotion of its binding.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 319 (1982), S. 101-107 
    ISSN: 1432-1912
    Keywords: Palytoxin ; Ouabain ; Erythrocytes ; Permeability ; ATPase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Palytoxin in concentrations as low as 1 pM raises the potassium permeability of rat, human and sheep erythrocytes, and the sodium permeability of human erythrocytes. The release of potassium or sodium from human cells also occurs when extracellular sodium is replaced by choline. 2. Ouabain inhibits the release due to palytoxin of potassium ions from human, sheep and rat erythrocytes, and also the release of sodium ions from human cells. The glycoside effect is specific since a) it is already prominent with 5×10−8 M ouabain b) rat erythrocytes are less sensitive than human cells to ouabain c) potassium release due to amphotericin B or the Ca2+ ionophore A23187 is not influenced by ouabain and d) dog erythrocytes are resistant to palytoxin as well as to ouabain. 3. Palytoxin has no direct influence on the Na+, K+-ATPase. It inhibits the binding of [3H]ouabain to erythrocyte membranes within the same concentration range as unlabelled ouabain. It partially displaces bound [3H]ouabain, and partially inhibits the inactivation of erythrocyte ATPase by the glycoside. Depletion of ATP or of external Ca2+ renders the cells less sensitive to palytoxin. Nevertheless inhibition by ouabain can be still demonstrated with human cells whose ATP stores had been largely exhausted, and also in the absence of external Ca2+. 4. Palytoxin decreases the surface tension at the air-water interface. We assume that the formation of nonspecific pores by palytoxin is linked with its surface activity. Further experiments should demonstrate whether ouabain prevents the binding of palytoxin to erythrocytes (“receptor hypothesis”), or whether an ouabain-sensitive hydrolysis of trace amounts of ATP (“metabolic hypothesis”) promotes the palytoxin effect.
    Type of Medium: Electronic Resource
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