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  • 1980-1984  (3)
  • Brain  (2)
  • Permeability
  • 1
    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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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 54 (1983), S. 61-70 
    ISSN: 1432-0738
    Keywords: Calmodulin ; Ca2+ ; Pb2+ ; Phosphodiesterase ; Phosphorylation ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have studied the interaction between some heavy metal ions, as compared with earth alkali ions, and calmodulin, a tissue protein which binds Ca2+ and mediates some of its effects. 1. Calmodulin dependent phosphodiesterase was activated with Pb2+, Ca2+, Sr2+, Ba2+, and Cd2+ (EC50 about 0.8 μM). The maximal activation achieved decreases in the order given. Hg2+ Sn2+, Fe2+, Cu2+, Ni2+, Bi3+, and Sb3+ up to 20 μM did not activate. 2. Pb2+ can replace Ca2+ with respect to the calmodulin-dependent phosphorylation of brain membranes. With high Pb2+ concentrations, phosphorylation was inhibited. 3. Calmodulin binding to brain membranes was enhanced with concentrations below 10−4 M in the following order: Pb2+ ≧Ca2+ ∼ Sr2+ 〉 Cd2+ 〉 Mn2+ 〉 Ba2+. In contrast Mg2+, Hg2+, Sn2+, Fe2+, Ni2+, Co2+, and Cu2+ triggered, if at all, a non-saturable binding of calmodulin. 4. In the flow-dialysis, other ions competed with 45Ca2+ binding to calmodulin in the following order: Pb2+ ∼ Ca2+ 〉 Mn2+, Ba2+, Cd2+, Sr2+. Thus among the ions investigated Pb2+ is a fully potent substitute for Ca2+ in every calmodulin-dependent reaction investigated. Cd2+ is always much less potent. The earth alkali ions Sr2+ and Ba2+ take an intermediate position. It remains to be shown whether calmodulin is merely a storage site for Pb2+, or whether the resulting functional changes play a role in Pb2+ poisoning.
    Type of Medium: Electronic Resource
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  • 3
    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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