Effects of chronic choleretic infusions of bile acids on the membrane of the bile canaliculus. A biochemical and morphologic study.

To determine whether choleretic infusions of bile acids modified the function or structure of the membrane of the bile canaliculus, sodium taurocholate (NaTc) or dehydrocholate (DHC) was infused into male rats at a rate of 80 mumoles per hour over an 18-hour period. Bile was collected by fistula and phospholipid and cholesterol content was measured in bile, liver homogenates, and isolated liver plasma membranes (LPM) enriched in bile canaliculi. Na+, K+-ATPase, Mg2+-ATPase, 5'-nucleotidase, and alkaline phosphatase activities were also measured in LPM. NaTc infusions enhanced cholesterol and phospholipid output in the bile in association with a significant increase in phospholipid in both LPM and liver homogenate. Although DHC infusions resulted in a comparable excretion of bile acid, phospholipid and cholesterol output in bile did not increase from control values and the concentration of these lipids in LPM and liver homogenate also did not change. However, LPM Na+, K+-ATPase significantly increased after DHC infusions compared to NaTc-infused animals or controls. Neither bile acid altered the activities of Mg2+-ATPase, 5'-nucleotidase, or alkaline phosphatase. Both bile acids increased the diameter of the lumen of the bile canaliculus as assessed by scanning electron microscopy and produced irregularities and outpouchings in the canalicular membrane. Diverticuli and loss of microvilli were most prominent with DHC infusions whereas canalicular side branching and the density of microvilli, either remained unchanged or increased following NaTc infusions. Although the morphologic findings are qualitative, the results of these studies indicate that chronic choleretic infusions of NaTc and DHC have divergent effects, not only on enzyme activities in liver plasma membrane, but on phospholipid composition and 3-dimensional structure. These findings suggest that bile acids may after biliary secretion not only through their osmotic effects, but by modifying lipids and enzymes in the membrane of the bile canaliculus.