ResearchBasic science: ObstetricsRole of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin
Section snippets
Chemicals
[3H]-rosiglitazone (specific activity, 50 Ci/mmol) and [14C]-metformin (specific activity, 50 mCi/mmol) were purchased from American Radiolabeled Chemicals, Inc (St. Louis, MO), and [3H]-glyburide (specific activity, 44.6 Ci/ mmol) from Perkin-Elmer (Boston, MA). All other chemicals were purchased from Sigma-Aldrich (Dallas, TX) unless otherwise noted.
Clinical material
Placentas from uncomplicated term pregnancies were obtained immediately after vaginal or abdominal deliveries from the labor and delivery ward of
Glyburide transport
The total ATP-dependent uptake of [3H]-glyburide, at its concentration of 100 nM, by placental IOVs was 3.2 ± 0.3 pmol/mg protein × minute. Inhibition of P-gp by verapamil decreased [3H]-glyburide uptake by 9 ± 5%. Inhibition of BCRP by 25 nM KO143 decreased [3H]-glyburide uptake by 25 ± 5%. Inhibition of MRP1 by indomethacin decreased [3H]-glyburide uptake by 43 ± 4%. Total inhibition of P-gp, BCRP, and MRP1 using 1 μM KO143 decreased [3H]-glyburide uptake by 78 ± 4%. The contributions of each
Comment
The goal of this investigation was to better understand the role of human placenta in fetal exposure to hypoglycemic drugs used in the treatment of GDM. To achieve this goal, we determined the activity of placental ABC transporters in the efflux of glyburide, rosiglitazone, and metformin using IOV preparations obtained from placental apical membranes. Because of the reversed orientation of the transporters within the IOVs, transporter uptake of a drug into inverted vesicles represents its
Acknowledgments
We thank the Perinatal Research Division for their assistance and the Publication, Grant, and Media Support of the UTMB Department of Obstetrics and Gynecology.
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Supported by the Obstetric-Fetal Pharmacology Research Unit (OPRU) Network (no. U10H0047891).
Cite this article as: Hemauer SJ, Patrikeeva SL, Nanovskaya TN, et al. Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin. Am J Obstet Gynecol 2010;202:383.e1-7.