Are novel scavenger-like receptors involved in the hepatic uptake of heparin?
Heparin is an anionic macromolecular drug. It has been widely used as an anticoagulant, and numerous efforts to clarify the mechanism of its disposition in the body have been made to help expand its clinical applications, using its newly found biological activities, as well as to further improve its use in anticoagulant therapy. It has now been shown that heparin is taken up extensively not only by Kupffer cells but also by parenchymal cells in the liver, the major distribution organ, and a receptor-mediated endocytotic mechanism, which is shared by heparin analogs and various anionic macromolecules, is responsible for heparin uptake in both types of cells. Although the characteristics of the receptors for heparin in both cells have lots of similarities to those of scavenger receptors, the receptors in parenchymal cells do not accept acetylated low density lipoprotein (Ac-LDL) as a ligand, which is the only striking difference between them and major scavenger receptors. Although the receptors in Kupffer cells, which accept Ac-LDL as a ligand, may belong to class A scavenger receptors, this remains to be established. We therefore conclude at present that it is likely that novel scavenger-like receptors for heparin (heparin receptors) or unidentified scavenger receptors are responsible for heparin uptake in the liver.
Yuasa
Hiroaki
H
Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan. yuasa@phar.nagoya-cu.ac.jp
Watanabe
Jun
J