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.

CONCLUSION

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.