The effects of bile acids on pancreatic ductal cells

Abstract

Bile acids (BAs) are natural end products of cholesterol metabolism (12). The physiological functions of BAs are the emulsification of lipid aggregates and solubilization of lipids in an aqueous environment. The major BAs in humans are chenodeoxycholic acid (CDCA) and cholic acid (CA), which are known as primary BAs since they are synthesized in the liver (46). Before secretion by hepatocytes, primary BAs are conjugated with either taurine or glycine, which increases their polarity and water solubility. Secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA) are produced in the colon by bacterial dehydroxylation of the primary BAs. Under physiological conditions, BAs are temporarily stored in the gallbladder and are released to the intestine. Most of the BAs are then efficiently reabsorbed from the ileum and transported back to the liver via the portal vein (enterohepatic circulation). Under normal, physiological conditions, BAs cannot get into the pancreas. However, under pathophysiological conditions, such as obstruction of the ampulla of Vater by an impacted gallstone, bile can enter into the pancreatic ducts and trigger pancreatitis (32). Unfortunately, we do not know the concentration of bile acids that can reach the pancreatic ductal cells under pathological conditions. It probably varies among patients and mainly depends on the duration of ampullary gallstone obstruction. However, previous studies have shown that relatively low concentrations of BAs (25-200 μM) are able to cause intracellular Ca signalling and cell death in acinar cells (23, 49). The close relationship between the passage of a gallstone and the development of acute pancreatitis (AP) has been known for more than a hundred years (32) and has been confirmed in a number of studies (30, 33, 45). However; the pathogenesis underlying the development of biliary AP is not well understood.