TY - JOUR
T1 - Receptor-mediated uptake of human α1-acid glycoprotein into liver parenchymal cells in mice
AU - Matsumoto, Kazuaki
AU - Nishi, Koji
AU - Kikuchi, Mari
AU - Watanabe, Hiroshi
AU - Nakajou, Keisuke
AU - Komori, Hisakazu
AU - Kadowaki, Daisuke
AU - Suenaga, Ayaka
AU - Maruyama, Toru
AU - Otagiri, Masaki
N1 - Funding Information:
Acknowledgments: This research was supported Grants-in-aid in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) (18590035 and 20390161).
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Asialoglycoprotein receptor (ASGPR)
KW - Galactose
KW - Oligosaccharide chain
KW - Pharmacokinetics
KW - Sialic acid
KW - α1-acid glycoprotein (AGP)
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U2 - 10.2133/dmpk.25.101
DO - 10.2133/dmpk.25.101
M3 - Article
C2 - 20208393
AN - SCOPUS:77949292288
SN - 1347-4367
VL - 25
SP - 101
EP - 107
JO - Drug Metabolism and Pharmacokinetics
JF - Drug Metabolism and Pharmacokinetics
IS - 1
ER -