Organic Solute Transporter, OSTα-OSTβ: Its Role in Bile Acid Transport and Cholestasis (original) (raw)

ABSTRACT

Organic solute transporter alpha-beta (OSTα-OSTβ) 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 E2. 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. OSTα-OSTβ 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 OSTα-OSTβ 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 OSTα-OSTβ in cholestasis.

KEYWORDS

Bile acid homeostasis - ileal bile acid transporter - adaptive regulation - nuclear receptor

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Carol J SorokaPh.D.

Department of Internal Medicine–Digestive, Yale University School of Medicine

333 Cedar Street/1080 LMP, P.O. Box 208019, New Haven, CT 06520-8019

Email: carol.soroka@yale.edu