Contribution of parenchymal and non-parenchymal liver cells to the clearance of hepatocyte growth factor from the circulation in rats.
OBJECTIVE
The distribution of 125I-hepatocyte growth factor (HGF) to either liver parenchymal cells (PC) or non-parenchymal cells (NPC) was investigated in rats.


METHODS
After injection of a trace amount of 125I-HGF, the distribution of radioactivity determined by microautoradiography closely resembled that of 125I-epidermal growth factor which distributes mainly to PC.


RESULTS
The uptake clearance of 125I-HGF estimated by determining the radioactivity of isolated liver cells was three times higher for PC than for NPC. This suggests that HGF distributes mainly to PC at relatively low doses. On the other hand, the uptake clearance by PC fell on coadministering an excess (80 micrograms/kg) of unlabeled HGF, while no change was observed for NPC, indicating that a saturable process for the hepatic handling of HGF exists only in PC where the HGF receptor is expressed.


CONCLUSIONS
At such a dose the uptake clearance was comparable for both PC and NPC showing that HGF distributes to both cell types although NPC have few HGF receptors. Since the distribution to NPC was relatively non-specific and heparin-sensitive, it may be that heparin-like substances, which are believed to exist on PC and/or the extracellular matrix, also exist on NPC.
Liu
K X
KX
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Kato
Y
Y
Terasaki
T
T
Aoki
S
S
Okumura
K
K
Nakamura
T
T
Sugiyama
Y
Y
D000818:Animals; D001345:Autoradiography; D002469:Cell Separation; D017364:Collagenases; D006493:Heparin / Q000493:pharmacokinetics; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D006493:Heparin; D017364:Collagenases