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Postcholestatic alkaline phosphatase activity after relief of bile duct obstruction in the rat
Author(s) -
Wielandt Ana Maria,
Pizarro Margarita,
Solis Nancy,
Arrese Marco,
Accatino Luigi
Publication year - 1993
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840180127
Subject(s) - alkaline phosphatase , cholestasis , medicine , endocrinology , bile duct , bile acid , enzyme , chemistry , enzyme assay , biliary tract , acid phosphatase , biology , biochemistry
The effects of obstructive cholestasis on the activity of alkaline phosphatase have been extensively studied in serum and liver tissue. However, very little is known about the activity of this enzyme in the postcholestatic condition after relief of the biliary obstruction. The purpose of this study has been to characterize alkaline phosphatase activity in serum, liver and bile in the postcholestatic period and to relate it to changes in bile acid secretory rate. Serum activity and biliary secretory rates of alkaline phosphatase were markedly increased in rats subjected to a reversible obstructive cholestasis for 24 hr or 48 hr and progressively declined along the postcholestatic period to values not significantly different from those of control rats within 48 hr. A significant direct linear relationship between the biliary secretory rates of enzyme activity and bile salts was apparent both in cholestatic groups and in the control groups. The slope of the regression line (units of alkaline phosphatase secreted per micromole of bile salts) was 1.5‐fold to 3‐fold higher in cholestatic animals. Remarkably, a positive y‐intercept of regression lines suggested that a significant fraction of the enzyme was secreted independently of bile salts; this fraction was 18‐fold and 34‐fold greater in 24‐hr and 48‐hr cholestatic rats, respectively, compared with that in controls. Sodium taurocholate 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 activity secreted per micromole of taurocholate was significantly greater 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 that a marked increase of alkaline phosphatase secretion into bile occurs in the postcholestatic condition. It presents further evidence for bile acid dependency of this process and demonstrates that more enzyme is secreted per micromole of bile salt in the postobstructive condition, probably related to the increased enzyme content in the liver and to an increased lability of the canalicular membrane enzyme to the solubilizing effect of secreted bile acids in cholestatic rats. In addition, this study suggests that alkaline phosphatase might be normally secreted into bile by another process independent of bile salts, which appears to be quantitatively more important in cholestatic than in control rats. (H EPATOLOGY 1993;18:179–187).