Change in hepatic handling of hepatocyte growth factor during liver
regeneration in rats.
Liu, Ke-Xin, Yukio Kato, Tetsuya Terasaki, Toshikazu Nakamura, and
Yuichi Sugiyama.
Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113, and Biomedical Research Center, Osaka
University School of Medicine, Suita, Osaka 565, Japan
APStracts 2:0142G, 1995.
The change in the hepatic uptake clearance of hepatocyte growth factor
(HGF) during liver regeneration in rats was examined. The hepatic
uptake clearance per g liver of 125I-HGF in vivo decreased to a
minimum level only 15 min after partial hepatectomy (PH). In the
perfused liver, in which the effect of endogenous substances can be
ignored, the hepatic uptake clearance of 125I-HGF did not change
until at least 3 hours after PH, suggesting that the decrease in the
clearance in vivo is caused by some endogenous inhibitors. Such a
decrease in the clearance cannot be explained only by the elevated
endogenous HGF concentration in plasma. In addition, at 48 h after PH
the decrease in hepatic uptake clearance was comparable for in vivo
and perfused liver (approx. a 50% and 60% reduction, respectively),
suggesting that the decreased hepatic clearance in vivo at that time
was caused mainly by reduction in the binding and/or uptake by the
liver itself. In addition, the hepatic uptake clearance of 125I-HGF
at that time in the presence of an excess (135 pM) of unlabeled HGF
was comparable with that of the control, indicating that only the
saturable portion of hepatic uptake clearance is reduced. The
internalization rate constant representing the probability of cell
-surface bound 125I-HGF being internalized per unit time increased to
three times that of the control at 15 min after PH, demonstrating
that the internalization of HGF is enhanced immediately after the
start of liver regeneration.
Received 14 June 1994; accepted in final form 14 June 1995.
APS Manuscript Number G228-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.