A variety of factors influence canalicular or ductal processes determining bile formation and its modification. Vagal stimulation, cholecystokinin, and gastrin weakly stimulate hepatic bile production, secretin potently stimulates ductule bile flow (increasing bicarbonate secretion), glucagon modestly stimulates canalicular bile formation and ductule bicarbonate secretion, and somatostatin potently inhibits bile secretion (canalicular and ductular sites).
The spectrum of effects of drugs on bile flow remains largely unexplored. A few drugs are known to modulate bile formation at the canalicular level by inducing transport pump activity (ie, multidrug resistance-associated protein-2 or MRP-2). Examples include certain glucocorticoids (and steroid hormones) and structurally unrelated xenobiotics, such as rifampicin, phenobarbital, oltipraz, and cisplatin.
It is also known that MRP-2 activity is downregulated by cholestasis. Furosemide has been shown to stimulate bile flow in the dog; however, it can impose a detrimental effect in the event of drug-induced dehydration.
A brisk choleresis can be induced by ursodeoxycholic acid and dehydrocholic acid, and they have been specifically studied in dogs. Oral ursodeoxycholic acid (UDCA; 50 mg/kg) increased bile flow by 70% within 1 hour, as well as the concentration of phospholipid, cholesterol, bile acids, and bilirubin in bile. Oral dehydrocholic acid (50 mg/kg) produced a considerable increase in bile flow (270%) by increasing secretion of electrolytes and water.
In human beings, UDCA decreases biliary cholesterol and increases HCO3-.
