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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 689-723 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Recent studies have revealed the import role played by transporters in the renal and hepatobiliary excretion of many drugs. These transporters exhibit a broad substrate specificity with a degree of overlap, suggesting the possibility of transporter-mediated drug-drug interactions with other substrates. This review is an overview of the roles of transporters and the possibility of transporter-mediated drug-drug interactions. Among the large number of transporters, we compare the Ki values of inhibitors for organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) and their therapeutic unbound concentrations. Among them, cephalosporins and probenecid have the potential to produce clinically relevant OAT-mediated drug-drug interactions, whereas cyclosporin A and rifampicin may trigger OATP-mediated ones. These drugs have been reported to cause drug-drug interactions in vivo with OATs or OATP substrates, suggesting the possibility of transporter-mediated drug-drug interactions. To avoid adverse consequences of such transporter-mediated drug-drug interactions, we need to be more aware of the role played by drug transporters as well as those caused by drug metabolizing enzymes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: epidermal growth factor ; receptor-mediated endocytosis ; transcytosis ; Madin-Darby Canine Kidney (MDCK) epithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this study is to clarify the intracellular fate and a rate limiting step in transcytosis of epidermal growth factor (EGF) in Madin-Darby Canine Kidney (MDCK) epithelial cells. Methods. The kinetics of transcytosis of 125I-EGF was investigated. To examine the fate of EGF molecules bound to its receptor on the cell surface, 125I-EGF was prebound to the basal surface at 4°C, followed by extensive washing and subsequent incubation at 37°C in EGF-free medium. Results. Saturable transport of 125I-EGF through the cell monolayer could only be observed from the basal to apical side. Most (~90%) of the EGF molecules bound to the surface receptor are internalized with a half-life of 1−3 min, followed by intracellular degradation with a half-life of 20−50 min. The exocytosis of internalized EGF into the apical medium is much slower with a half-life of 130−250 min. Even when 125I-EGF was incubated with MDCK cells at 37°C and washed with acid to remove cell-surface 125I-EGF, intact 125I-EGF appeared in the basal medium with a half life of 160−170 min. Conclusions. The exocytosis of internalized EGF into the apical medium is a rate limiting step in EGF transcytosis. At least a small amount of internalized EGF is recycled.
    Type of Medium: Electronic Resource
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