Deletion of the ileal basolateral bile acid transporter identifies the cellular sentinels that regulate the bile acid pool

Davis, Roger J.; Attie, Alan D.

doi:10.1073/pnas.0801194105

Cited by 20 publications

(16 citation statements)

References 15 publications

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“…As predicted from this model, OST ␣ null mice had signifi cantly increased FGF15 expression and reduced hepatic Cyp7a1 expression ( 170,171 ). These fi ndings further supported a central role of FGF15/19 in regulating hepatic bile acid synthesis ( 243,244 ) as recently confi rmed in the liver and intestine-specifi c FXR and LRH-1 null mice and reviewed by the late Dr. Roger Davis ( 75,245,246 ).…”

Section: Renal Bile Acid Transportsupporting

confidence: 61%

Bile acid transporters

Dawson

Lan

Rao

2009

Journal of Lipid Research

593

456

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Section: Renal Bile Acid Transportsupporting

confidence: 61%

Bile acid transporters

Dawson

Lan

Rao

2009

Journal of Lipid Research

593

456

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“…FGF15/19 then signals at the hepatocyte to down-regulate hepatic bile acid synthesis. The net result is that hepatic bile acid synthesis is paradoxically repressed rather than induced, the normal physiological response to a block in intestinal bile acid absorption (Davis and Attie 2008; Rao et al 2008). …”

Section: The Basolateral Bile Acid and Organic Solute Transporter:mentioning

confidence: 99%

Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition

Dawson

2010

Handbook of Experimental Pharmacology

196

166

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Membrane transporters expressed by the hepatocyte and enterocyte play critical roles in maintaining the enterohepatic circulation of bile acids, an effective recycling and conservation mechanism that largely restricts these potentially cytotoxic detergents to the intestinal and hepatobiliary compartments. In doing so, the hepatic and enterocyte transport systems ensure a continuous supply of bile acids to be used repeatedly during the digestion of multiple meals throughout the day. Absorption of bile acids from the intestinal lumen and export into the portal circulation is mediated by a series of transporters expressed on the enterocyte apical and basolateral membranes. The ileal apical sodium-dependent bile acid cotransporter (abbreviated ASBT; gene symbol, SLC10A2) is responsible for the initial uptake of bile acids across the enterocyte brush border membrane. The bile acids are then efficiently shuttled across the cell and exported across the basolateral membrane by the heteromeric Organic Solute Transporter, OSTα-OSTβ. This chapter briefly reviews the tissue expression, physiology, genetics, pathophysiology, and transport properties of the ASBT and OSTα-OSTα. In addition, the chapter discusses the relationship between the intestinal bile acid transporters and drug metabolism, including development of ASBT inhibitors as novel hypocholesterolemic or hepatoprotective agents, prodrug targeting of the ASBT to increase oral bioavailability, and involvement of the intestinal bile acid transporters in drug absorption and drug-drug interactions.

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“…FXR in turn regulates the transcription of FGF15 (in rodents, FGF19 in man). FGF15 is secreted into the portal circulation and in the liver represses via a receptor mediated process the biosynthesis of bile salts [55,258]. In humans, reduced serum levels of FGF19 lead to bile salt induced diarrhea, which highlights the importance of a tight control of the bile salt pool [132,335].…”

Section: Physiology Of Bile Formationmentioning

confidence: 99%