Adaptive response of the enterohepatic circulation of bile acids to extrahepatic cholestasis.

Experimental cholestasis induced by ligation of the common bile duct results in morphological and functional changes in the rat hepatocyte. The aim of this study was to evaluate the adaptive response of the transport process involved in the enterohepatic circulation of bile salts to obstructive cholestasis. Male Sprague-dawley rats with common bile duct ligation were killed after 48 and 72 hours. Portal and systemic blood and duodenal aspirates were collected. Taurocholate transport was measured in isolated ileal brush border (BBM) and liver basolateral membranes (BLM). Drastic reduction in intraluminal bile salt concentrations in ligated rats accompanied decreases in saturable taurocholate uptake by ileal BBMs. Kinetic analysis indicated that the decrease was attributable to reduction in transporter density and alteration in affinity for the substrate, both of which accentuated with increase in postligation time. In contrast, despite 20-fold higher portal venous bile salt concentrations, taurocholate uptake by hepatic sinusoidal membrane was lower in rats. Kinetic analysis and immunoblots developed using polyclonal antisera to the liver BLM bile acid transporter demonstrated a gradual decrease in transporter density with increase in postligation time accompanied by reduced taurocholate uptake by basolateral membrane. These results further support the concept that the ileal brush border membrane transporter is regulated by the availability of the substrate, whereas regulation of the bile salt transport across the liver BLM is independent of portal venous bile acid concentration.