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Cited by 8Metabolism and Genetic DisordersDrug Transport and Resistance MechanismsAmino Acid Enzymes and Metabolism

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

Up-Regulation of Carnitine Transporters Helps Maintain Tissue Carnitine Levels in Carnitine Deficiency Induced by Pivalic Acid

Okudaira, Noriko, Fujigaki, Masao, Nakayoshi, Takemi, Komiya, Izumi, Sugiyama, Yuichi·2001·Pharmaceutical Research
DOI 10.1023/a:1011042008169
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Abstract

Purpose Pivalic acid (PVA) forms conjugates with endogenous carnitine and enhances its excretion. The purpose of this study is to determine whether tissue carnitine levels decrease in parallel with plasma levels in carnitine deficiency induced by PVA.Methods PVA was orally administered to rats for 5 days. Carnitine levels in plasma, liver, kidney, muscle, and heart were monitored. The tissue uptake clearance (CLuptake) was determined in vivo by the integration plot method. Hepatocytes were prepared from control and PVA-treated rats, and the uptake of L-carnitine was determined.Results Plasma concentrations of L-carnitine decreased as a result of the enhanced carnitine elimination as pivaloylcarnitine (PCN) when rats were treated with PVA. However, L-carnitine concentrations in liver, muscle, and heart remained relatively constant during the study. period. CLuptake increased in liver and muscle and, thus, the rate of carnitine uptake from plasma into these tissues did not change even at low plasma concentrations. This helps maintain carnitine levels in these tissues. Up-regulation of carnitine transporters is suggested to be a mechanism for the increased CLuptake.Conclusions In the carnitine deficiency state induced by PVA, increased CLuptake owing to up-regulation of carnitine transporters is suggested to help maintain carnitine levels in some tissues.

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Crossref · 10.1023/a:1011042008169

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Citations

Cites

Research works printed but not linked: 2

  1. R. Fujii, K. Sunakawa, T. Yokota, Y. Nitta, H. Akita, S. Iwata, Y. Satoh, H. Meguro, H. Satoh, K. Niino, Y. Toyonaga, N. Iwai, H. Nakamura, Y. Kobayashi, M. Kino, H. Higashino, H. Kamiya, K. Kitamura, M. Ito, T. Nishikawa, H. Tada, A. Maruo, and S. Yamamoto. Safety and carnitine status after oral administration of S-1108 to pediatric patients. Chemotherapy 41:655-665 (1993).
  2. Y. Sawada. Physiological parameters in humans and animals. In M. Hanano, K. Umemura, and T. Iga (eds.), Applied Pharmacokinetics—Theory and Experiments, Soft Science, Inc., Tokyo, Japan, 1985 pp. 433-449.

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Metadata

Authors
Okudaira, N., Fujigaki, M., Nakayoshi, T., Komiya, I., & Sugiyama, Y.
Affiliations
  • Meiji Seika Pharma Co., Ltd. (Japan) (JP)
  • The University of Tokyo (JP)
Corresponding author
Okudaira, Noriko
Venue
Pharmaceutical Research
Publisher
Springer Science and Business Media LLC
Published
2001-04
Volume
18
Issue
4
Pages
439-445
ISSN
  • 0724-8741 (ISSN-L)
  • 1573-904X
DOI
10.1023/a:1011042008169
OpenAlex
W1499536514
Cited by
8
References
29
Citations by year
2016: 1 · 2014: 1 · 2013: 1
FWCI
0.18
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Pharmaceutical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
carnitine deficiency, pivalic acid, carnitine transporter, L-carnitine, plasma carnitine
MeSH terms
Solute Carrier Family 22 Member 5, Animals, Carnitine, Carrier Proteins, Injections, Intra-Arterial, Injections, Intravenous, Male, Pentanoic Acids, Tissue Distribution, Up-Regulation, Rats, Sprague-Dawley, Organic Cation Transport Proteins, Rats

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