Importance of the liver in plasma clearance of hepatocyte growth factors in rats

Am J Physiol. 1992 Nov;263(5 Pt 1):G642-9. doi: 10.1152/ajpgi.1992.263.5.G642.


After intravenous administration of 125I-labeled hepatocyte growth factor (HGF), trichloroacetic acid-precipitable radioactivity in the plasma disappeared rapidly with an early phase half-life of 4 min. The amounts of 125I-HGF distributed to the liver, adrenal, spleen, kidney, and lung tissues were much greater than those that could be accounted for by distribution to the extracellular space alone. The first-pass removal of 125I-HGF by the liver was approximately 26%; the liver accounted for approximately 70% of early-phase removal. The hepatic handling was also analyzed using a single-pass perfused liver system. The steady-state extraction ratio of tracer 125I-HGF was 0.48 but dropped to 0.23 in the presence of excess HGF (135 pM), demonstrating hepatic removal saturation of HGF. In the presence of excess HGF, the heparin-washable 125I-HGF, the heparin-resistant and acid-washable 125I-HGF, and the internalized 125I-HGF dropped to 54, 31, and 32% of the control values. The presence of at least two binding sites for HGF on the liver cell surfaces was made clear: the heparin-washable site and the heparin-resistant and acid-washable binding site, considered to have higher affinity for HGF. The internalization of 125I-HGF was observed to some extent even in the presence of excess HGF and phenylarsine oxide, known to be an inhibitor of polypeptides receptor-mediated endocytosis, suggesting the contribution of a relatively nonspecific internalization mechanism as well as receptor-mediated endocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism
  • Hepatocyte Growth Factor / blood*
  • Hepatocyte Growth Factor / metabolism
  • Kinetics
  • Liver / metabolism*
  • Male
  • Perfusion / methods
  • Rats
  • Rats, Wistar
  • Tissue Distribution


  • Hepatocyte Growth Factor