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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 313 (1980), S. 85-89 
    ISSN: 1432-1912
    Keywords: Isolated hepatocytes ; Phalloidin poisoning ; Iopodate, iodipamide ; Bile acid transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several anionic substances used for cholecystography inhibit the development of protrusions in isolated hepatocytes in response to phalloidin. Drugs from the iopodate family were equieffective with those of the iodipamide type. The above protective effect results from a competitive inhibition of the phallotoxin uptake as shown for iopodate. Cholecystographic agents similarily inhibit the inward transport of cholic acid in a competitive manner. The inhibition of the phallotoxin response is inversely correlated with the uptake of 3H-demethylphalloin (r=0.94) and with the inward transport of cholate (r=0.84) at various inhibiting concentrations of iopodate.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 317 (1981), S. 364-367 
    ISSN: 1432-1912
    Keywords: Isolated hepatocytes ; Phalloidin ; Ligandin ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To exclude an involvement of ligandin in the uptake and storage of phalloidin in hepatocytes equilibriumdialysis studies were made with phalloidin, cholic acid and bromosulfophthalein (BSP). Binding studies with isolated ligandin indicated that the affinity of ligandin for phalloidin is low (K D=0.8×10−3 M). Phalloidin neither displaced BSP (K D=1.3×10−7M) or cholic acid (K D=7.6×10−5 M) from ligandin, when preloaded with these substrates. Hepatocytes prepared from rats after daily treatment with phenobarbital during 5 days contained 3–4-fold concentrations of ligandin and bound greater amounts of BSP than controls. Nevertheless the velocity of the uptake both of [3H]-demethylphalloin ([3H]-DMP) and of [35S]-BSP was not augmented. Also the sensitivity of liver cells to phalloidin was not drastically modified after induction with phenobarbital and agrees with earlier findings in vivo. We conclude that ligandin plays a negligible role in the uptake and a minor role in the storage of phallotoxins in liver cells.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 44 (1980), S. 99-105 
    ISSN: 1432-0738
    Keywords: Newborn rats ; Isolated hepatocytes ; Phalloidin ; 3H-Demethylphalloin ; Bile acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A method is described for the preparation of isolated hepatocytes from 5 day old rats, based on the procedure of Berry and Friend (1969). In contrast to the original procedure the liver of newborn rats was perfused in the reverse direction from the vena cava caudalis (pars thoracalis) to the vena portae. The cells obtained by the above method are morphologically intact as shown by electron micrographs and by phase contrast microscopy. About 85% of the isolated cells excluded trypan blue. Neonatal liver cell preparations were used for dose response studies with phallotoxins and further experimental applications in the field of phalloidin tolerance of newborns are described.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 307 (1979), S. 275-281 
    ISSN: 1432-1912
    Keywords: Phalloidin uptake ; Isolated hepatocytes ; Baby rats ; Regenerating liver ; Phallodin antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 3H-Demethylphalloin (3H-DMP) a cyclopeptide very similar to phalloidin is taken up by isolated hepatocytes in vitro. Hepatocytes prepared from newborn animals are less sensitive to phalloidin. Their uptake of 3H-DMP is about one tenth of that of cells from adult animals. Ascites hepatoma cells, known to be insensitive to phalloidin took up negligible amounts of 3H-DMP. Cells prepared from regenerating livers took up insignificantly lower amounts of the toxin than in hepatocytes from adult animals. Treatment of hepatocytes with low concentrations of trypsin was found to switch off the phalloidin sensitivity in a reversible manner. This inhibition is due to a reduced uptake of 3H-DMP. Pretreatment of animals with CCl4, known to reduce the sensitivity to phalloidin, also decreases the uptake of 3H-DMP in isolated hepatocytes. Various agents, drugs and reagents were found to inhibit the response of isolated hepatocytes to phalloidin. All these compounds (bile acids, rifampicin, silybin, DIDS, glutardialdehyde, bromosulphophthalein, fusidic acid, antamanide, novobiocin) inhibit also the uptake of 3H-DMP in isolated hepatocytes. The results confirm our working hypothesis, presented in several previous papers, that decreased sensitivity to phalloidin is probably due to a reduced or blocked uptake of the toxin.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1912
    Keywords: Isolated hepatocytes ; Diethylnitrosamine ; Phallotoxin sensitivity ; Bile acid uptake ; 3H-Demethylphalloin uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated hepatocytes prepared from rats pretreated with diethylnitrosamine (0.5 mg/kg DENA/day p.o.) are less sensitive to phalloidin poisoning. They take up lower amounts of both phallotoxins and bile acids than controls. The degree of inhibition depends on the period of pretreatment.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 311 (1980), S. 91-94 
    ISSN: 1432-1912
    Keywords: Phalloidin ; Phalloin ; Demethylphalloin ; Isolated hepatocytes ; Uptake kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The uptake of trace amounts of 3H-demethylphalloin (3H-DMP) by isolated hepatocytes was studied in the presence of various concentrations of unlabeled demethylphalloin (DMP), of phalloin and of phalloidin. The addition of phalloidin (or phalloin) reduces the uptake of 3H-DMP more than the addition of the equivalent concentration of DMP. The error caused by dilution of 3H-DMP with phalloin or phalloidin is not constant and depends on the concentration of the unlabeled compound. The relative differences between the uptake of 3H-DMP in the presence of demethylphalloin and in the presence of either phalloin or phalloidin cannot be explained by a competitive model. Some consequences for the use of 3H-DMP in toxicokinetic experiments are discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 319 (1982), S. 249-253 
    ISSN: 1432-1912
    Keywords: Isolated hepatocytes ; Phallotoxin uptake ; Bile salt transport ; Covalently coupling derivatives of bile salts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of covalently binding derivatives of bile acids, fusidic acid and of compounds similar to cholecystographic agents were synthesized. Nearly all of them inhibited the development of protrusions on the surface of isolated hepatocytes regularly seen after treatment with phalloidin. The same compounds inhibited the uptake of demethylphalloin and of cholate in a concentration dependent manner. Two kinds of effects could be distinguished: The irreversible part of the inhibition depended on the incubation period and could not be removed by washing procedures. The reversible one was independent on the duration of the preincubation. Final results indicated that the tested derivatives inhibited either both transports, and the phalloidin response of liver cells to the same degree and in the same manner, or were found to be ineffective in all tests. The above parallelism supports the hypothesis that phallotoxins may be translocated by a carrier system normally responsible for the uptake of bile acids from the portal blood.
    Type of Medium: Electronic Resource
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