Intracellular disposition of polysaccharides in rat liver parenchymal and nonparenchymal cells.
Binding and internalization of arabinogalactan, pullulan, dextran, and mannan were examined in rat liver parenchymal and nonparenchymal cells using 125I or fluorescein isothiocyanate (FITC) labeled polysaccharides. Binding and uptake of arabinogalactan and pullulan into parenchymal cells was inhibited by asialofetuin, indicating that the asialoglycoprotein receptor is involved in the intracellular disposition of arabinogalactan and pullulan. Uptake of 125I-labeled dextran to parenchymal cells was unchanged upon addition of excess unlabeled dextran, suggesting that dextran uptake occurs via fluid phase endocytosis. Of the polysaccharides tested, mannan showed the strongest specific association with liver nonparenchymal cells. FITC-labeled polysaccharides showed arabinogalactan and pullulan are internalized to liver parenchymal cells, whereas mannan is internalized to nonparenchymal cells. This study demonstrates that intracellular disposition of polysaccharides in the liver occurs via receptor-mediated endocytosis (RME), indicating that RME plays a role in the biodisposition of these polysaccharides as drug carriers.
Tanaka
Tetsuro
T
Department of Biopharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Sanzo, Ichi-banchi, Gakuen-cho, Fukuyama 729-0292, Japan. tanaka@fupharm.fukuyama-u.ac.jp
Fujishima
Yuko
Y
Hanano
Shinya
S
Kaneo
Yoshiharu
Y
D000818:Animals; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003911:Dextrans / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007457:Iodine Radioisotopes; D007564:Japan; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D011134:Polysaccharides / Q000145:classification / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D013678:Technology, Pharmaceutical / Q000379:methods
D003911:Dextrans; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D016650:Fluorescein-5-isothiocyanate