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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 320-326 
    ISSN: 1432-1912
    Schlagwort(e): Rat liver ; Transport of organic cations ; OCT1 ; Type I hepatic transport of cationic drugs ; 1-Methyl-4-phenylpyridinium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The kidneys and the liver are the principal organs for the inactivation of circulating organic cations. Recently, an organic cation transporter (OCT1) has been cloned from rat kidney. In order to answer the question whether OCT1 is involved also in hepatic uptake of organic cations, the pharmacological characteristics of organic cation transport in hepatocytes were compared to the characteristics of transiently expressed OCT1. Primary cultures of rat hepatocytes avidly accumulated the small organic cation 3H-1-methyl-4-phenylpyridinium (3H-MPP+). At equilibrium, the hepatocytes accumulated 3H-MPP+ 56-fold. Initial rates of specific 3H-MPP+ transport in hepatocytes were saturable. The half-saturating concentration was 13 μmol/l. 3H-MPP+ transport was sensitive to quinine (Ki = 0.79 μmol/l) and cyanine863 (Ki = 0.097 µmol/l). Quinine and cyanine863 are known inhibitors of type I hepatic transport of cationic drugs and of renal excretion of organic cations, respectively. To compare the functional characteristics of 3H-MPP+ transport in hepatocytes with those of OCT1, OCT1 has been heterologously expressed and characterized in a mammalian cell line (293 cells). Initial rates of 3H-MPP+ transport were saturable, the Km being 13 μmol/l. The rank order of inhibitory potencies of various inhibitors was almost identical in hepatocytes and 293 cells transiently transfected with OCT1. There was a positive correlation between the Ki's for the inhibition of 3H-MPP+ transport in isolated hepatocytes and transfected 293 cells (r = 0.85; P〈0.01; n = 8). The results indicate that OCT1 is functionally expressed not only in the kidney but also in hepatocytes where it is responsible for the transport of small organic cations which, in the past, have been classified as type I substrates.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 320-326 
    ISSN: 1432-1912
    Schlagwort(e): Key words Rat liver ; Transport of organic cations ; OCT1 ; Type I hepatic transport of cationic drugs ; 1-Methyl-4-phenylpyridinium
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The kidneys and the liver are the principal organs for the inactivation of circulating organic cations. Recently, an organic cation transporter (OCT1) has been cloned from rat kidney. In order to answer the question whether OCT1 is involved also in hepatic uptake of organic cations, the pharmacological characteristics of organic cation transport in hepatocytes were compared to the characteristics of transiently expressed OCT1. Primary cultures of rat hepatocytes avidly accumulated the small organic cation 3H-1-methyl-4-phenylpyridinium (3H-MPP+). At equilibrium, the hepatocytes accumulated 3H-MPP+ 56-fold. Initial rates of specific 3H-MPP+ transport in hepatocytes were saturable. The half-saturating concentration was 13 μmol/l. 3H-MPP+ transport was sensitive to quinine (Ki = 0.79 μmol/l) and cyanine863 (Ki = 0.097 μmol/l). Quinine and cyanine863 are known inhibitors of type I hepatic transport of cationic drugs and of renal excretion of organic cations, respectively. To compare the functional characteristics of 3H-MPP+ transport in hepatocytes with those of OCT1, OCT1 has been heterologously expressed and characterized in a mammalian cell line (293 cells). Initial rates of 3H-MPP+ transport were saturable, the Km being 13 μmol/l. The rank order of inhibitory potencies of various inhibitors was almost identical in hepatocytes and 293 cells transiently transfected with OCT1. There was a positive correlation between the Ki’s for the inhibition of 3H-MPP+ transport in isolated hepatocytes and transfected 293 cells (r = 0.85; P〈0.01; n = 8). The results indicate that OCT1 is functionally expressed not only in the kidney but also in hepatocytes where it is responsible for the transport of small organic cations which, in the past, have been classified as type I substrates.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Natural hazards 14 (1996), S. 227-240 
    ISSN: 1573-0840
    Schlagwort(e): Colorado dams ; earthquake recurrence ; probabilistic distances ; probabilistic seismic hazard analysis ; peak horizontal acceleration ; acceleration response spectra
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Energietechnik , Geographie , Geologie und Paläontologie
    Notizen: Abstract A seismic hazard evaluation for three dams in the Rocky Mountains of northern Colorado is based on a study of the historical seismicity. To model earthquake occurrence as a random process utilizing a maximum likelihood method, the catalog must exhibit random space-time characteristics. This was achieved using a declustering procedure and correction for completeness of recording. On the basis of the resulting a- and b-values, probabilistic epicentral distances for a 2 × 10−5 annual probability were calculated. For a random earthquake of magnitude M L 6.0–6.5, this distance is 15 km. Suggested ground motion parameters were estimated using a probabilistic seismic hazard analysis. Critical peak horizontal accelerations at the dams are 0.22g if median values are assumed and 0.39g if variable attenuation and seismicity rates are taken into account. For structural analysis of the dams, synthetic acceleration time series were calculated to match the empirical response spectra. In addition, existing horizontal strong motion records from two Mammoth Lakes, California earthquakes were selected and scaled to fit the target horizontal acceleration response spectra.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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