Ileal sodium/bile acid cotransporter explained

Ileal sodium/bile acid cotransporter, also known as apical sodium–bile acid transporter (ASBT) and ileal bile acid transporter (IBAT), is a protein that in humans is encoded by the SLC10A2 gene.^{[1] [2]}

ASBT/IBAT is most highly expressed in the ileum, where it is found on the brush border membrane of enterocytes. It is responsible for the initial uptake of bile acids, particularly conjugated bile acids, from the intestine as part of their enterohepatic circulation.^[3]

As a drug target

Several medications to inhibit IBAT are under development. They include elobixibat, under development for the treatment of constipation and irritable bowel syndrome,^[4] and volixibat, under development for the treatment of nonalcoholic steatohepatitis.

See also

• Solute carrier family

References

Further reading

• Shneider BL . Intestinal bile acid transport: biology, physiology, and pathophysiology . Journal of Pediatric Gastroenterology and Nutrition . 32 . 4 . 407–17 . April 2001 . 11396803 . 10.1097/00005176-200104000-00002 . free .
• Balakrishnan A, Polli JE . Apical sodium dependent bile acid transporter (ASBT, SLC10A2): a potential prodrug target . Molecular Pharmaceutics . 3 . 3 . 223–30 . 2006 . 16749855 . 2796132 . 10.1021/mp060022d .
• Wong MH, Oelkers P, Dawson PA . Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity . The Journal of Biological Chemistry . 270 . 45 . 27228–34 . November 1995 . 7592981 . 10.1074/jbc.270.45.27228 . free.
• Oelkers P, Kirby LC, Heubi JE, Dawson PA . Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2) . The Journal of Clinical Investigation . 99 . 8 . 1880–7 . April 1997 . 9109432 . 508012 . 10.1172/JCI119355 .
• Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA . Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter . The American Journal of Physiology . 274 . 1 Pt 1 . G157-69 . January 1998 . 10.1152/ajpgi.1998.274.1.G157 . 9458785 .
• Montagnani M, Love MW, Rössel P, Dawson PA, Qvist P . Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption . Scandinavian Journal of Gastroenterology . 36 . 10 . 1077–80 . October 2001 . 11589382 . 10.1080/003655201750422693 . 218908622 .
• Love MW, Craddock AL, Angelin B, Brunzell JD, Duane WC, Dawson PA . Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia . Arteriosclerosis, Thrombosis, and Vascular Biology . 21 . 12 . 2039–45 . December 2001 . 11742882 . 10.1161/hq1201.100262 . free .
• Jung D, Fried M, Kullak-Ublick GA . Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha . The Journal of Biological Chemistry . 277 . 34 . 30559–66 . August 2002 . 12055195 . 10.1074/jbc.M203511200 . free .
• Zelcer N, Saeki T, Bot I, Kuil A, Borst P . Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co-transfected with the ileal Na+-dependent bile-acid transporter . The Biochemical Journal . 369 . Pt 1 . 23–30 . January 2003 . 12220224 . 1223054 . 10.1042/BJ20021081 .
• Neimark E, Chen F, Li X, Shneider BL . Bile acid-induced negative feedback regulation of the human ileal bile acid transporter . Hepatology . 40 . 1 . 149–56 . July 2004 . 15239098 . 10.1002/hep.20295 . free .
• Xia X, Roundtree M, Merikhi A, Lu X, Shentu S, Lesage G . Degradation of the apical sodium-dependent bile acid transporter by the ubiquitin-proteasome pathway in cholangiocytes . The Journal of Biological Chemistry . 279 . 43 . 44931–7 . October 2004 . 15304498 . 10.1074/jbc.M400969200 . free.
• Zhang EY, Phelps MA, Banerjee A, Khantwal CM, Chang C, Helsper F, Swaan PW . Topology scanning and putative three-dimensional structure of the extracellular binding domains of the apical sodium-dependent bile acid transporter (SLC10A2) . Biochemistry . 43 . 36 . 11380–92 . September 2004 . 15350125 . 10.1021/bi049270a .
• Banerjee A, Ray A, Chang C, Swaan PW . Site-directed mutagenesis and use of bile acid-MTS conjugates to probe the role of cysteines in the human apical sodium-dependent bile acid transporter (SLC10A2) . Biochemistry . 44 . 24 . 8908–17 . June 2005 . 15952798 . 10.1021/bi050553s .
• Nakahara M, Furuya N, Takagaki K, Sugaya T, Hirota K, Fukamizu A, Kanda T, Fujii H, Sato R . Ileal bile acid-binding protein, functionally associated with the farnesoid X receptor or the ileal bile acid transporter, regulates bile acid activity in the small intestine . The Journal of Biological Chemistry . 280 . 51 . 42283–9 . December 2005 . 16230354 . 10.1074/jbc.M507454200 . free .
• Bergheim I, Harsch S, Mueller O, Schimmel S, Fritz P, Stange EF . Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers . Journal of Lipid Research . 47 . 1 . 42–50 . January 2006 . 16237211 . 10.1194/jlr.M500215-JLR200 . free .
• Banerjee A, Swaan PW . Membrane topology of human ASBT (SLC10A2) determined by dual label epitope insertion scanning mutagenesis. New evidence for seven transmembrane domains . Biochemistry . 45 . 3 . 943–53 . January 2006 . 16411770 . 2525805 . 10.1021/bi052202j .

Notes and References

1. Wong MH, Rao PN, Pettenati MJ, Dawson PA . Localization of the ileal sodium-bile acid cotransporter gene (SLC10A2) to human chromosome 13q33 . Genomics . 33 . 3 . 538–40 . May 1996 . 8661017 . 10.1006/geno.1996.0233 .
2. Web site: Entrez Gene: SLC10A2 solute carrier family 10 (sodium/bile acid cotransporter family), member 2.
3. Book: Dawson PA . Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition . Drug Transporters . Handbook of Experimental Pharmacology . 201 . 169–203 . 2011 . 201 . 21103970 . 3249407 . 10.1007/978-3-642-14541-4_4 . 978-3-642-14540-7 .
4. Acosta A, Camilleri M . Elobixibat and its potential role in chronic idiopathic constipation . Therapeutic Advances in Gastroenterology . 7 . 4 . 167–75 . July 2014 . 25057297 . 4107709 . 10.1177/1756283X14528269 .