Document Detail

Pleiotropic functions of the organic solute transporter Ostα-Ostβ.
MedLine Citation:
PMID:  21691099     Owner:  NLM     Status:  MEDLINE    
The heteromeric organic solute transporter alpha-beta (Ostα-Ostβ) is expressed at relatively high levels on the basolateral membrane of enterocytes, where it plays a critical role in the intestinal absorption of bile acids and the enterohepatic circulation. However, this transporter is also expressed in nearly all human tissues, including those that are not normally thought to be involved in bile acid homeostasis, indicating that Ostα-Ostβ may have additional roles beyond bile acid transport in these other tissues, or that bile acids and their derivatives are more pervasive than currently envisioned. Emerging data from different laboratories provide support for both of these hypotheses. In particular, recent studies indicate that tissues such as brain and ovary have the capacity to synthesize bile acids or bile acid precursors. In addition, studies examining Ostα-Ostβ substrate specificity have revealed that this transporter can also accept conjugated steroids, including some neurosteroids, and that the transporter is selectively expressed in steroidogenic cells of the brain and adrenal gland, suggesting a novel function for Ostα-Ostβ. The broad tissue expression of Ostα-Ostβ is also consistent with the emerging concept that bile acids and their derivatives act as signaling molecules in diverse tissues. Bile acids activate nuclear receptors such as the farnesoid X receptor (FXR/NR1H4), the pregnane X receptor and the vitamin D receptor, are ligands for a G-protein-coupled bile acid receptor (GPBAR1/TGR5), and can also activate protein kinases A and C as well as mitogen-activated protein kinase pathways. These signaling pathways are present in many tissues and regulate processes such as triglyceride, glucose and energy homeostasis. Note that although FXR and TGR5 are thought to function primarily as bile acid receptors, they are modulated by some other sterols and select lipid metabolites, and are also widely expressed in tissues, indicating a complex interplay among diverse regulatory networks that impact critical cell and organ functions. The present report summarizes the evidence for a pleiotropic role of Ostα-Ostβ in different tissues.
Nazzareno Ballatori
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2011-06-17
Journal Detail:
Title:  Digestive diseases (Basel, Switzerland)     Volume:  29     ISSN:  1421-9875     ISO Abbreviation:  Dig Dis     Publication Date:  2011  
Date Detail:
Created Date:  2011-06-21     Completed Date:  2011-10-28     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  8701186     Medline TA:  Dig Dis     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  13-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, N.Y., USA.
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MeSH Terms
Bile Acids and Salts / metabolism
Membrane Transport Proteins / metabolism*
Organ Specificity
Receptors, Cytoplasmic and Nuclear / metabolism
Sterols / metabolism
Grant Support
Reg. No./Substance:
0/Bile Acids and Salts; 0/Membrane Transport Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/Sterols

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