THE EFFECT OF COMPLETE BILIARY OBSTRUCTION ON BILE SECRETION - STUDIES ON THE MECHANISMS OF POSTCHOLESTATIC CHOLERESIS IN THE RAT
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Date
1981
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Abstract
Rats subjected to obstructive cholestasis apparently demonstrate in the postcholestatic period, after common duct obstruction release, a marked increase in canalicular bile flow relative to bile acid excretion. Changes in canalicular permeability and in (Na+-K+)-ATPase activity in isolated liver surface membranes were studied to determine whether they are associated with postcholestatic choleresis. The clearances of 14C-erythritol and 3H-inulin were simultaneously measured in rats subjected to a 3 day obstructive cholestasis and in controls, during spontaneous choleresis as well as during the i.v. infusion of sodium taurocholate at submaximal and saturating rates. In additional groups of bile duct-ligated rats and controls, liver surface membrane fractions were isolated and the activity of appropriate marker enzymes and (Na+-K+)-ATPase was determined. In the 2 groups 14C-erythritol clearance closely approximated total bile flow, suggesting that bile flow was of canalicular origin. Cholestatic rats showed a 6-fold increase in 3H-inulin clearance compared to controls. Canalicular permeability to inulin is apparently markedly increased in cholestatic rats. (Na+-K+)-ATPase activity was significantly higher in cholestatic rats than in controls in the homogenate (P < 0.001) and liver surface membranes, (P < 0.001). Enhanced choleretic response to bile acids in the postcholestatic period is associated with an increased permeability of canalicular structure to inulin and with a significant increase in homogenate and surface membrane (Na+-K+)-ATPase activity. Some important differences between bile secretory function of rats subjected to obstructive cholestasis and that described in models of bile secretory failure induced by drugs or monohydroxy-bile acids, are pointed out.