In experimental bile obstruction the serum activities of the membrane-bound liver
enzymes,
alkaline phosphatase,
5'-nucleotidase and
gamma-glutamyltransferase are greatly increased, whereas in the liver only the
alkaline phosphatase activity is elevated. After partial
hepatectomy or tetrachloride
poisoning the
alkaline phosphatase activity in the regenerating live is increased to the same extent as in
cholestasis without an accompanying elevation in serum activity. The following results support the hypothesis of a
bile salt-mediated solubilization of membrane-bound
enzymes in cholestatic liver: (1) 30 min after bile duct
ligation the total
bile acids in the liver were increased 5-fold, 2 h later as much as 10-fold. After 1 day, the
bile acid concentration was still 4 times above normal. (2) Isolated plasma membranes from normal and obstructed livers were incubated in vitro with increasing amounts of tri- and dihydroxycholanic
acids. At a final concentration of 1 mmol/l
taurochenodeoxycholate significant amounts of membrane-bound
enzymes were released into the 12,000-g supernatant. (3) In the regenerating liver, where tissue phsophatase activity was high and serum
phosphatase activity unchanged, the
bile salt concentration was not increased.