POSTCHOLESTATIC ALKALINE-PHOSPHATASE ACTIVITY AFTER RELIEF OF BILE-DUCT OBSTRUCTION IN THE RAT

The effects of obstructive cholestasis on the activity of alkaline pho sphatase have been extensively studied in serum and liver tissue. Howe ver, very little is known about the activity of this enzyme in the pos tcholestatic condition after relief of the biliary obstruction. The pu rpose of this study has been to characterize alkaline phosphatase acti vity in serum, liver and bile in the postcholestatic period and to rel ate it to changes in bile acid secretory rate. Serum activity and bili ary secretory rates of alkaline phosphatase were markedly increased in rats subjected to a reversible obstructive cholestasis for 24 hr or 4 8 hr and progressively declined along the postcholestatic period to va lues not significantly different from those of control rats within 48 hr. A significant direct linear relationship between the biliary secre tory rates of enzyme activity and bile salts was apparent both in chol estatic groups and in the control groups. The slope of the regression line (units of alkaline phosphatase secreted per micromole of bile sal ts) was 1.5-fold to 3-fold higher in cholestatic animals. Remarkably, a positive y-intercept of regression lines suggested that a significan t fraction of the enzyme was secreted independently of bile salts; thi s fraction was 18-fold and 34-fold greater in 24-hr and 48-hr cholesta tic rats, respectively, compared with that in controls. Sodium tauroch olate administered intravenously, either as a bolus or as an infusion at increasing submaximal rates, resulted in parallel increases of bile salt and alkaline phosphatase secretory rates into bile. The enzyme a ctivity secreted per micromole of taurocholate was significantly great er in cholestatic than in control rats. In the liver tissue, increased homogenate and canalicular membrane alkaline phosphatase activity in 24-hr cholestatic rats progressively decreased to reach control values 48 hr after relief of biliary obstruction. This study demonstrates th at a marked increase of alkaline phosphatase secretion into bile occur s in the postcholestatic condition. It presents further evidence for b ile acid dependency of this process and demonstrates that more enzyme is secreted per micromole of bile salt in the postobstructive conditio n, probably related to the increased enzyme content in the liver and t o an increased lability of the canalicular membrane enzyme to the solu bilizing effect of secreted bile acids in cholestatic rats. In additio n, this study suggests that alkaline phosphatase might be normally sec reted into bile by another process independent of bile salts, which ap pears to be quantitatively more important in cholestatic than in contr ol rats.