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    Characterization of Dextromethorphan And Dextrorphan Uptake by a Putative Glutamic Acid Carrier and Passive Diffusion Across Brain Microvessel Endothelium

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    Issue Date
    1993
    Author
    Shi, Fenglin
    Cavitt, Jennifer
    Bailey, Carole A.
    Malick, Waseem A.
    Audus, Kenneth L.
    Publisher
    Informa Healthcare
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    The mechanisms of uptake and transcellular passage of dextromethorphan (DM) and its major metabolite dextrorphan (DX) across the endothelial component of the blood–brain barrier have been investigated with primary cultures of bovine brain microvessel endothelial cells (BMECs). The uptake of [14C]DM and [14C]DX by BMECs was observed to be temperature-sensitive and saturable, with approximate Km's of 0.12 and 0.29 mM and Vmax's of 9.2 and 11.0 pmol/mg/min, respectively. The BMEC uptake of [14C] DM was inhibited half-maximally by approximately 0.57 mM L-glutamic acid, 0.71 mM N-methyl-d-asparatate (NMDA), and 0.99 mM DL-threo-β-hydroxyaspartic acid. The BMEC uptake of [14C]DX was inhibited half-maximally by approximately 0.48 mM L-glutamic acid, 1.50 mM NMDA, and 0.69 mM DL-threo-β-hydroxyaspartic acid. Conversely, the bidirectional passage of DM and DX across confluent BMEC monolayers occurred at a faster rate but was neither saturable nor inhibited by high concentrations of glutamic acid, NMDA, or unlabeled DM or DX. These results suggest that DM and DX are capable of interacting with a low-capacity glutamic acid-type carrier mechanism on the apical surface of BMECs. However, the net transfer of these agents across BMEC monolayers appeared to be more rapid and passive in nature.
    Description
    Read More: http://informahealthcare.com/doi/abs/10.3109/10717549309022764
    URI
    http://hdl.handle.net/1808/7612
    DOI
    https://doi.org/10.3109/10717549309022764
    Collections
    • Pharmacy Scholarly Works [286]
    Citation
    Shi, F., Cavitt, J.L., Bailey, C., Malick, A.W., and Audus, K.L. (1993) Characterization of dextromethorphan and dextrorphan uptake by a putative glutamic acid carrier and passive diffusion across brain microvessel endothelium. Drug Delivery 1, 113-118. http://dx.doi.org/10.3109/10717549309022764

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    KU Libraries
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    KU Libraries
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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