Watanabe J, Haba M, Yuasa H
Faculty of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan.
Pharm Res. 1995 Jul;12(7):1092-5. doi: 10.1023/a:1016235120585.
The uptake of fractionated 3H-heparin by isolated rat Kupffer cells was examined to determine the uptake mechanism.
The association of fractionated 3H-heparin was concentration-dependent with a dissociation constant of 3.4 nM and a maximum association capacity of 1.3 pmol/10(6) cells, suggesting the involvement of a specialized mechanism. Although 2,4-dinitrophenol inhibited neither the association nor internalization of fractionated 3H-heparin, lowering the temperature from 37 degrees C to 4 degrees C reduced the internalization of fractionated 3H-heparin by 70% without affecting the association.
It is suggested that the uptake mechanism may differ from receptor-mediated endocytosis of polypeptides and be mediated by scavenger receptors, because organic anions, and several ligands of scavenger receptors, as well as several heparin analogs, inhibit the binding of fractionated 3H-heparin to Kupffer cells, while phenylarsine oxide, which is known to inhibit the receptor-mediated or absorptive endocytosis of polypeptides, inhibits neither the association nor internalization of fractionated 3H-heparin.
检测分离的大鼠枯否细胞对分次给予的3H-肝素的摄取，以确定摄取机制。
分次给予的3H-肝素的结合呈浓度依赖性，解离常数为3.4 nM，最大结合容量为1.3 pmol/10(6)细胞，提示存在一种特殊机制。虽然2,4-二硝基苯酚既不抑制分次给予的3H-肝素的结合也不抑制其内化，但将温度从37℃降至4℃可使分次给予的3H-肝素的内化减少70%，而不影响结合。
提示摄取机制可能不同于多肽的受体介导的内吞作用，而是由清道夫受体介导，因为有机阴离子、清道夫受体的几种配体以及几种肝素类似物可抑制分次给予的3H-肝素与枯否细胞的结合，而氧化苯胂已知可抑制多肽的受体介导的或吸附性内吞作用，但既不抑制分次给予的3H-肝素的结合也不抑制其内化。
