Intestinal bile acid transport: biology, physiology, and pathophysiology.
Intestinal reabsorption of bile salts plays a crucial role in human health and disease. This process is primarily localized to the terminal ileum and is mediated by a 48-kd sodium-dependent bile acid cotransporter (SLC10A2 = ASBT). ASBT is also expressed in renal tubule cells, cholangiocytes, and the gallbladder. Exon skipping leads to a truncated version of ASBT, which sorts to the basolateral surface and mediates efflux of bile salts. Inherited mutation of ASBT leads to congenital diarrhea secondary to bile acid malabsorption. Partial inhibition of ASBT may be useful in the treatment of hypercholesterolemia and intrahepatic cholestasis. During normal development in the rat ileum, ASBT undergoes a biphasic pattern of expression with a prenatal onset, postnatal repression, and reinduction at the time of weaning. The bile acid responsiveness of the ASBT gene is not clear and may be dependent on both the experimental model used and the species being investigated. Future studies of the transcriptional and posttranscriptional regulation of the ASBT gene and analysis of ASBT knockout mice will provide further insight into the biology, physiology, and pathophysiology of intestinal bile acid transport.
Shneider
B L
BL
Mount Sinai Medical Center, New York, NY 10029, USA.
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D003967:Diarrhea / Q000209:etiology / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology*; D029363:Organic Anion Transporters, Sodium-Dependent; D051381:Rats; D012964:Sodium / Q000378:metabolism; D027981:Symporters; D014886:Weaning
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; D012964:Sodium