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

研究成果: Article査読

8 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)101-107
ページ数7
ジャーナルDrug Metabolism And Pharmacokinetics
25
1
DOI
出版ステータスPublished - 2010
外部発表はい

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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