title: Receptor-mediated uptake of human alpha1-acid glycoprotein into liver parenchymal cells in mice.
abstract: Human alpha(1)-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.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Nishi
authors.forename: Mari
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakajou
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Komori
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.forename: Ayaka
authors.initials: A
authors.lastname: Suenaga
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000187:drug effects; D001212:Asialoglycoproteins / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D009961:Orosomucoid; C018203:agalacto-orosomucoid; C017030:asialoorosomucoid