Involvement of Carnitine/organic Cation Transporter OCTN2 (SLC22A5) in Distribution of its Substrate Carnitine to the Heart
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- IWATA Daisuke
- Division of Pharmaceutical Sciences, Graduate School of Natural Science & Technology, Kanazawa University
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- KATO Yukio
- Division of Pharmaceutical Sciences, Graduate School of Natural Science & Technology, Kanazawa University
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- WAKAYAMA Tomohiko
- Department of Histology and Embryology, Graduate School of Medical Science, Kanazawa University
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- SAI Yoshimichi
- Division of Pharmaceutical Sciences, Graduate School of Natural Science & Technology, Kanazawa University
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- KUBO Yoshiyuki
- Division of Pharmaceutical Sciences, Graduate School of Natural Science & Technology, Kanazawa University
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- ISEKI Shoichi
- Department of Histology and Embryology, Graduate School of Medical Science, Kanazawa University
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- TSUJI Akira
- Division of Pharmaceutical Sciences, Graduate School of Natural Science & Technology, Kanazawa University
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Abstract
This study was designed to clarify the pharmacological role of carnitine/organic cation transporter (Octn) family members in mouse heart. Immunohistochemical analysis revealed that Octn1 was exclusively expressed on endothelial cells in blood vessels. Octn2 was detected on the plasma membrane of cardiac muscle cells by immunoelectron microscopy. Octn3 was not detected in the heart. Integration plot analysis showed that coadministration of unlabeled L-carnitine reduced distribution of L-[3H]carnitine to the heart. L-[3H]Carnitine uptake in heart slices was reduced by carnitine analogs and various Octn2 substrates. L-[3H]Carnitine uptake by heart slices from juvenile visceral steatosis (jvs) mice, which have a hereditary octn2 gene deficiency, was negligible. Distribution of [3H]quinidine, another Octn2 substrate, to the heart was not reduced by L-carnitine, and [3H]quinidine uptake in heart slices was Na--independent and inhibited by cationic drugs, but not carnitine analogs. [3H]Quinidine uptake by heart slices from jvs mice was similar to that of wild-type mice. These results demonstrate that OCTN2 is functionally expressed on the plasma membrane of muscle cells and is involved in distribution of carnitine to the heart. Some mechanism(s) other than OCTN2 is involved in the distribution of quinidine to the heart.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 23 (3), 207-215, 2008
The Japanese Society for the Study of Xenobiotics
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Details 詳細情報について
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- CRID
- 1390001205178431872
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- NII Article ID
- 10024188374
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- NII Book ID
- AA1162652X
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- ISSN
- 18800920
- 13474367
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed