Organic solute transporter, OSTalpha-OSTbeta: its role in bile acid transport and cholestasis.
Organic solute transporter alpha-beta (OSTalpha-OSTbeta) is a unique heteromeric transporter localized to the basolateral membrane of epithelial cells involved in sterol transport. It is believed to be the primary bile acid efflux transporter in the intestine of mammals and is therefore essential to bile acid homeostasis and the enterohepatic circulation. First described in the evolutionarily primitive small skate, LEUCORAJA ERINACEA, this facilitated transporter requires expression of both subunits for its function. It can transport a variety of bile acids, as well as estrone 3-sulfate, dehydroepiandrosterone 3-sulfate, digoxin, and prostaglandin E (2). Expression of both subunits is variable between species and tissues; in humans high expression is noted in the liver, small intestine, kidney, testis, and adrenal gland. OSTalpha-OSTbeta is directly regulated by the bile acid sensing nuclear receptor, farnesoid X receptor (FXR). Furthermore, it is part of the complex regulatory pathway that controls bile acid synthesis and homeostasis. Hepatic OSTalpha-OSTbeta is upregulated in cholestasis in both humans and rodents, where it appears to play a protective role. Additional studies are necessary to determine its role in liver injury, bile acid malabsorption, and lipid and glucose metabolism, as well as a potential protective role for kidney OSTalpha-OSTbeta in cholestasis.
Soroka
Carol J
CJ
Department of Internal Medicine and Yale Liver Center, Yale University School of Medicine, New Haven Connecticut 06520-8019, USA. carol.soroka@yale.edu
Ballatori
Nazzareno
N
Boyer
James L
JL
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002779:Cholestasis / Q000503:physiopathology*; D004764:Enterohepatic Circulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D013379:Substrate Specificity / Q000502:physiology
D018435:ATP Binding Cassette Transporter, Subfamily B; D001647:Bile Acids and Salts; D026901:Membrane Transport Proteins; C476575:organic solute transporter alpha, human; C476576:organic solute transporter alpha, mouse; C476577:SLC51B protein, human; C476578:organic solute transporter beta, mouse