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    Modulation of P-glycoprotein activity in Calu-3 cells using steroids and β-ligands

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    Audus_AFD_Hamilton et al Int J Pharm 2001.pdf (241.4Kb)
    Issue Date
    2001
    Author
    Hamilton, Karen O.
    Yazdanian, Mehran
    Audus, Kenneth L.
    Publisher
    Elsevier
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Metadata
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    Abstract
    The purpose of this work was to investigate if P-glycoprotein (Pgp) efflux pump activity could be inhibited in the sub-bronchial epithelial cell line, Calu-3, by glucocorticosteroids and β-ligands. The Pgp modulation efficiency of each compound was determined by its ability to increase the accumulation of the Pgp substrate rhodamine 123 (Rh123) accumulation in these cells. Pgp inhibition was observed at ≥ 100 μM steroids and β-ligand. The modulation effectiveness of the β-ligands increased with increasing hydrophobicity (log Poctanol/aqueous) whereas an obvious correlation was not obtained with the complete set of steroids tested. Steroidal Pgp substrates did not affect Rh123 accumulation (e.g., aldosterone, dexamethasone, 11β, 17α, 21-OH progesterone). In contrast, two hydrophobic non P-gp steroidal substrates (testosterone and progesterone) displayed different effects on Rh123 accumulation, with progesterone being the more potent modulator. The most hydrophobic β-ligand, propranolol, a known Pgp substrate, gave the largest increase in Rh123 accumulation in this therapeutic class. The β-ligand modulation efficiency could also be correlated to Pgp structural recognition elements such as hydrogen bonding potential, the presence of a basic nitrogen and planar aromatic ring. No effect on Rh123 accumulation was observed with the formulation additives tested (ethanol, glycerol and palmitoyl carnitine) at concentrations previously reported to be non-toxic to Calu-3 cells.
    Description
    Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.
    URI
    http://hdl.handle.net/1808/7487
    DOI
    https://doi.org/10.1016/S0378-5173(01)00836-5
    Collections
    • Pharmacy Scholarly Works [286]
    Citation
    Hamilton, K.O., Yazdanian, M., and Audus, K.L. (2001) Modulation of P-glycoprotein activity in Calu-3 cells using steroids and b-ligands. Int. J. Pharm. 228, 171-179. PMID: 11576779 http://dx.doi.org/10.1016/S0378-5173(01)00836-5

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    785-864-8983
    KU Libraries
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    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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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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