Bile formation is a crucial function of the liver. Bile is produced by hepatocytes and reaches via bile ducts the small intestine, where it assists in the digestion and absorption of fat. Bile salts are major constituents of bile. Bile salts are detergents and hence are potentially toxic to hepatocytes. The canalicular membrane of hepatocytes contains microdomains (or lipid rafts), which may serve to protect this membrane from the detergent action of bile salts. These microdomains are rich in cholesterol and sphingolipids and also contain ATP-binding cassette (ABC) transporters, which export bile constituents from hepatocytes into the canaliculus. The transport rate of ABC transporters is augmented by an increased membrane cholesterol content. This mechanism may be an additional element protecting the canalicular membrane from the detergent action of bile salts. It is well established that drugs inhibiting the transport activity of the bile salt export pump BSEP may lead to liver injury. Similarly, drugs interfering with canalicular lipid secretion can also lead to liver injury, highlighting the importance of the canalicular lipids for protecting hepatocytes from the detergent action of bile salts.
Bruno Stieger, PhD is senior research associate at the Department of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland. He holds a PhD in biochemistry from the Federal Institute of Technology in Zurich Switzerland. The Department of Clinical Pharmacology and Toxicology has cloned the major bile salt and drug transport systems of hepatocytes. The current research interests of the department relate to i) understanding the role of the interaction of drugs with transport systems in the development of acquired liver disease, ii) investigating molecular mechanisms of canalicular lipid secretion and iii) studying the regulation of transporter expression.