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Thyroid Hormone Regulates the Expression and Function of P-glycoprotein in Caco-2 Cells

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Abstract

Purpose

In patients with thyroid disorders, abnormalities in the pharmacokinetics of various drugs including digoxin, a substrate of P-glycoprotein (Pgp) which plays a crucial role in drug absorption and disposition, have been reported. In this study, we examined the effect of 3,5,3′-l-triiodothyronine (T3) on the function and expression of Pgp using the human intestinal epithelial cell line Caco-2.

Materials and Methods

The effect of T3 on the expression of Pgp and MDR1 mRNA was assessed by Western blotting and competitive polymerase chain reaction, respectively. Digoxin uptake and transport by Pgp was assessed using Caco-2 cell monolayers.

Results

The expression of MDR1 mRNA was increased by T3 treatment in a concentration-dependent manner. Pgp expression was also increased by 100 nM T3, whereas it decreased on depletion of T3. The amount of [3H]digoxin accumulated in Caco-2 cell monolayers treated with T3 was diminished significantly compared with that in control cells. In addition, the basal-to-apical transcellular transport of [3H]digoxin was accelerated by T3 treatment.

Conclusions

These results indicate that T3 regulates the expression and function of Pgp. It is possible that changes in Pgp expression alter the pharmacokinetics of Pgp substrates in patients with thyroid disorders.

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Abbreviations

PCR:

polymerase chain reaction

Pgp:

P-glycoprotein

T3 :

3,5,3′-l-triiodothyronine

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Acknowledgments

This work was supported in part by the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science”, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by The Nakatomi Foundation. N. N. is supported as a Teaching Assistant by the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science.”

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  1. Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan

    Naoki Nishio, Toshiya Katsura & Ken-ichi Inui

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  1. Naoki Nishio
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  2. Toshiya Katsura
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  3. Ken-ichi Inui
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Correspondence to Ken-ichi Inui.

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Nishio, N., Katsura, T. & Inui, Ki. Thyroid Hormone Regulates the Expression and Function of P-glycoprotein in Caco-2 Cells. Pharm Res 25, 1037–1042 (2008). https://doi.org/10.1007/s11095-007-9495-x

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  • DOI: https://doi.org/10.1007/s11095-007-9495-x

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