Maximal hepatic bilirubin transport in the rat during somatostatin-induced cholestasis and taurocholate-choleresis

A steady maximal biliary secretion of bilirubin has been produced in male Wistar rats, recovered from anesthesia, by continuous infusion of 256 nmol of unconjugated bilirubin per hour per 100 gm body weight, after priming with 3.4 mumols. The administration of somatostatin (2 micrograms/hr/100 gm body weight) produced a reversible decrease of bile flow and bile acid excretion while bilirubin output was unchanged. After discontinuation of somatostatin, a slight increase in the output of bilirubin conjugates was observed with the rapid recovery of bile flow. Administration of Na+ taurocholate at increasing rates (30 to 480 nmol/min/100 gm body weight) progressively enhanced bile flow and bile acid secretion. The rate of secretion of bilirubin conjugates increased to 18% above the values in controls at a taurocholate dose of 120 nmol/min/100 gm body weight and remained at that level with higher amounts, in spite of further increases in flow. Under Na+ taurocholate, somatostatin failed to reverse the enhancement of bilirubin output, although it still inhibited the secretion of bile acids and bile flow. A mechanism linked to osmotic flow induced by taurocholate would appear to serve as a component of the total capacity of the hepatocyte to transfer bilirubin conjugates into the canaliculus. At low bile-acid secretory rates this component seems of minor quantitative importance, whereas a major (specific) pathway seems not yet saturated.