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Interaction of thiazolidinediones with renal organic cation transporters
Author(s) -
Soodvilai Sirima,
Soodvilai Sunhapas
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb757
Subject(s) - rosiglitazone , chinese hamster ovary cell , chemistry , transporter , organic cation transport proteins , pioglitazone , ic50 , inhibitory postsynaptic potential , pharmacology , organic anion transporter 1 , substrate (aquarium) , receptor , endocrinology , medicine , biochemistry , in vitro , biology , diabetes mellitus , gene , ecology , type 2 diabetes
We determined the interaction of TZDs on organic cation transporters (OCTs) in Chinese hamster ovary (CHO‐K1) cells stably transfected with rabbit (rb)OCT1 and rbOCT2, and in murine isolated renal cortical slices. Rosiglitazone but not pioglitazone inhibited uptake of 3H‐MPP+, a substrate of rbOCT1 and rbOCT2, via both transporters with half maximal inhibitory concentration (IC50) of rosiglitazone for rbOCT1‐ and rbOCT2‐ mediated MPP+ uptake of 7.4 μM and 2.5 μM, respectively. The mode of rosiglitazone inhibition was further determined using kinetic analysis. We showed that rosiglitazone decreased the maximal transport (Jmax) but without effect on the transporter affinity (Kt) indicating the inhibitory effect of rosiglitazone on rbOCT1 and rbOCT2 was noncompetitive manner. Similar to the effect seen in the cell‐cultured system, the inhibitory effect of rosiglitazone was also observed in intact renal cortical slices. Taken together, we concluded that rosiglitazone seemed to inhibit transport activity of OCT1 and OCT2 by interfering with non‐substrate‐ binding site of the transporters.