These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Human P-glycoprotein transports cyclosporin A and FK506.
    Author: Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T.
    Journal: J Biol Chem; 1993 Mar 25; 268(9):6077-80. PubMed ID: 7681059.
    Abstract:
    Cyclosporin A, a cyclic undecapeptide, and FK506 are efficient immunosuppressive agents. They also attract attention as effective P-glycoprotein modulators that inhibit P-glycoprotein from binding to anticancer drugs and overcome multidrug resistance. Cyclosporin A itself interacts with a common binding site of P-glycoprotein to which Vinca alkaloids and verapamil bind. We were interested to determine whether cyclosporin A and FK506 are substrates for P-glycoprotein to transport, and we studied their transcellular transport. In LLC-PK1 cells, derived from porcine kidney proximal tubule and forming a highly polarized epithelium, cyclosporin A was transported in a saturable manner. LLC-GA5-COL300, a transformant cell line derived by transfecting LLC-PK1 with human MDR1 cDNA isolated from normal adrenal gland, expresses P-glycoprotein specifically on the apical surface and shows a typical multidrug-resistant phenotype. LLC-GA5-COL300 cells showed increased transport of cyclosporin A from the basal to the apical side. Kinetic analysis showed that this transport was a typical saturable transport with the calculated apparent Michaelis constant (Kappm) and the maximum flux (Vmax) as 8.4 microM and 2.4 nmol/mg protein/h, respectively. LLC-GA5-COL300 also showed increased transport of FK506 from the basal to the apical side. These results indicate that P-glycoprotein transports the immunosuppressive agents cyclosporin A and FK506.
    [Abstract] [Full Text] [Related] [New Search]