Receptor-mediated uptake of human α1-acid glycoprotein into liver parenchymal cells in mice

Kazuaki Matsumoto, Koji Nishi, Mari Kikuchi, Hiroshi Watanabe, Keisuke Nakajou, Hisakazu Komori, Daisuke Kadowaki, Ayaka Suenaga, Toru Maruyama, Masaki Otagiri

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Human α1-acid glycoprotein (AGP), a serum glycoprotein, is thought to have anti-inflammatory effects by a mechanism that is not well understood. In this study, we investigated the pharmacokinetics of AGP in mice using enzymatically modified AGP (AGP with the sialic acids removed, asialo-AGP, and with both sialic acids and galactose removed, agalacto-AGP). It was observed that AGP was eliminated from the circulation slowly, and was mainly taken up by the liver. The elimination of labeled AGP, asialo-AGP and agalacto-AGP from the circulation was suppressed in the presence of excess unlabeled AGP, asialo-AGP and agalacto-AGP, respectively, suggesting the receptor-mediated uptake of these AGPs. Interestingly, the uptake of AGP by the liver competed with agalacto-AGP, but not with asialo-AGP, while agalacto-AGP competed with asialo-AGP. These results suggest that agalacto-AGP binds to at least two types of receptors, namely asialoglycoprotein receptor (ASGPR) and an as yet unidentified receptor that is shared with AGP, and that AGP is directly taken up by the liver through such a receptor and not via ASGPR. These findings help improve our understanding of the clearance mechanism of AGP.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalDrug Metabolism And Pharmacokinetics
Volume25
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1
Externally publishedYes

Keywords

  • Asialoglycoprotein receptor (ASGPR)
  • Galactose
  • Oligosaccharide chain
  • Pharmacokinetics
  • Sialic acid
  • α1-acid glycoprotein (AGP)

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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  • Cite this

    Matsumoto, K., Nishi, K., Kikuchi, M., Watanabe, H., Nakajou, K., Komori, H., Kadowaki, D., Suenaga, A., Maruyama, T., & Otagiri, M. (2010). Receptor-mediated uptake of human α1-acid glycoprotein into liver parenchymal cells in mice. Drug Metabolism And Pharmacokinetics, 25(1), 101-107. https://doi.org/10.2133/dmpk.25.101