Induction of rat hepatic and intestinal alkaline phosphatase activity produced by bile from bile duct-ligated animals

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Abstract
Bile duct ligation caused a 3-fold elevation of not only hepatic but also intestinal alkaline phosphatase. The increase was transient in intestinal mucosa and peaked at 12 h. Hepatic phosphatase levels reached a plateau by 36 h. I.p. injection of bile from ligated animals into normal rats produced qualitatively similar results. Studies were performed to further characterize the induction of phosphatase activity in both tissues. The addition of bile from ligated animals to organ explants of liver and intestine produced a 2- and 3-fold rise in activity, respectively. Therefore, neural and hormonal factors are not essential in producing this induction. The increased activity produced in vitro in both tissues was due to heat-stable and dialyzable factor(s) and was blocked by inhibitors of protein synthesis. In the intestine, activity occurred over the entire brush border as demonstrated by EM histochemistry. In the liver, increased activity was noted over the entire plasma membrane and was not localized to the canalicular membrane. Tunicamycin treatment of liver and intestinal explants markedly suppressed the induced phosphatase activity. Simultaneous treatment with protease inhibitors restored some of the phosphatase activity. Glycosylation of the alkaline phosphatase may provide at least partial protection from proteolysis.