Contribution of Parenchymal and Non-Parenchymal Liver Cells to the Clearance of Hepatocyte Growth Factor From the Circulation in Rats

Ke Xin Liu, Yukio Kato, Tetsuya Terasaki, Shoichi Aoki, Kazuo Okumura, Toshikazu Nakamura, Yuichi Sugiyama

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Purpose. 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 µg/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.

Original languageEnglish
Pages (from-to)1737-1740
Number of pages4
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Volume12
Issue number11
DOIs
Publication statusPublished - 1995 Nov
Externally publishedYes

Keywords

  • hepatocyte growth factor
  • liver
  • pharmacokinetics
  • receptor-mediated endocytosis

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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