Abstract
P-glycoprotein (Pgp) is expressed in various normal tissues and plays an important role in drug absorption and disposition. In addition, it is supposed that alterations in the expression levels of Pgp are involved in the inter- and intraindividual variability of pharmacokinetics of many drugs. Since pharmacokinetic properties of various drugs are altered in patients with thyroid disorders, we examined the expression of Pgp and mdr1a/1b mRNA in the kidney, liver, jejunum, and ileum from euthyroid and hyperthyroid rats. Western blot analysis revealed that Pgp expression was markedly increased in the kidney and liver of hyperthyroid rats. In contrast, it was slightly increased in the jejunum and ileum. mdr1a/1b mRNA levels were significantly increased in the kidney of hyperthyroid rats. However, they were not increased in the liver as well as in the jejunum and ileum of hyperthyroid rats. Expression levels of bile salt export pump and mdr2 mRNA were also unchanged in hyperthyroid rat liver. Taken together, these findings suggest that thyroid hormone induces Pgp expression in a tissue-selective manner, and that the modulation of mdr1a/1b mRNA expression in the hyperthyroid state varies among tissues.
Footnotes
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This work was supported in part by 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 21st Century Center of Excellence (COE) Program “Knowledge Information Infrastructure for Genome Science.”
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.004770.
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ABBREVIATIONS: Pgp, P-glycoprotein; T4, l-thyroxine; bsep, bile salt export pump; PCR, polymerase chain reaction.
- Received March 19, 2005.
- Accepted August 3, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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