Effect of galactose on binding and endocytosis of asialoglycoprotein in cultured rat hepatocytes.
BACKGROUND
99mTc-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) has been applied clinically in scintigraphy to estimate functioning liver mass, but it is not so sensitive in differentiating mild liver injury from normal liver. 99mTc-GSA is thought to bind to the asialoglycoprotein receptor (ASGP-R) and is then internalized and degraded in the hepatocytes. The aim of this study is to know whether D-galactose inhibits GSA binding or internalization to hepatocyes because ASGP-R recognizes galactose residues of ligands.


METHODS
Isolated rat hepatocytes were obtained by collagenase perfusion, pre-cultured for 2 h after plating, and then cultured for 16 to 18 h until use. The effect of galactose on GSA binding and internalization into cells was investigated by using cultured hepatocytes.


RESULTS
Galactose non-competitively inhibited GSA binding to cultured hepatocytes, but its Ki value was quite high (505 +/- 38 mM). Galactose significantly inhibited GSA internalization into hepatocytes at 27 mM.


CONCLUSIONS
It was clarified that D-galactose inhibited GSA internalization rather than binding at a low concentration. Further in vivo studies in rats are needed to know whether an administration of galactose prior to performing 99mTc-GSA scintigraphy can brake it possible to estimate the functioning mass in mild liver injury.
Hata
S
S
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Ishii
K
K
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005690:Galactose / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D011956:Receptors, Cell Surface; D013668:Technetium Tc 99m Aggregated Albumin; C070561:technetium Tc 99m DTPA-galactosyl-human serum albumin; D016284:Technetium Tc 99m Pentetate; D005690:Galactose