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  • 1
    ISSN: 1573-904X
    Keywords: nucleoside ; nucleoside transport ; brush border membrane vesicles ; sodium ion dependence ; adenosine, (human kidney)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na+-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na+-driven 3H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na+–uridine transport was determined. At a concentration of 100 µM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na+-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na+-uridine uptake with a K i of 26.4 µM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na+–nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The K i of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: taurine ; transport ; choroid plexus ; epithelium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Taurine, a β-amino acid, is a neuromodulator which interacts functionally with the glycinergic, GABAergic, cholinergic and adrenergic systems. Although a continuous cell culture model is not available for the choroid plexus epithelia, we recently described a primary cell culture of rabbit choroid plexus epithelia. The goal of the current study was to determine the suitability of this primary cell culture for the study of the Na+-taurine transporter in the rabbit choroid plexus. Methods. A primary cell culture of rabbit choroid plexus epithelial cells was grown on semi-permeable filters and kinetics of 3H-taurine uptake were ascertained. Results. Taurine transport in the cultured choroid plexus cells was Na+-dependent and saturable (Km = 156 μM). The β-amino acids, β-alanine and taurine, significantly inhibited Na+-driven taurine transport whereas L-alanine partially inhibited taurine transport in the cultured cells. In addition, we observed that the activity of the Na+-taurine transporter is affected by exposure to taurine in the media. Conclusions. These results demonstrate that a Na+-taurine transporter with characteristics similar to those in the intact tissue is expressed in cultured choroid plexus epithelial cells. The transporter may undergo adaptive regulation and play a role in taurine homeostasis in the central nervous system.
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  • 3
    ISSN: 1573-904X
    Keywords: choroid plexus ; epithelium ; Na+-dependent transport ; cell culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-904X
    Keywords: nucleosides ; transport ; choroid ; plexus ; human ; HIV
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 38 (1998), S. 431-460 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract Organic cation transporters are critical in drug absorption, targeting, and disposition. It has become increasingly clear that multiple mechanisms are involved in organic cation transport in the key tissues responsible for drug absorption and disposition: the kidney, liver, and intestine. In this review, we discuss current models of transepithelial flux of organic cations in these three tissues. Particular emphasis is placed on the more recent molecular studies that have paved the way for a more complete understanding of the physiological and pharmacological roles of the organic cation transporters. Such information is essential in predicting pharmacokinetics and pharmacodynamics and in the design and development of cationic drugs.
    Type of Medium: Electronic Resource
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