Mechanisms and regulation of bile secretion

Nathanson, Michael H.; Boyer, James L.

doi:10.1002/hep.1840140324

Cited by 381 publications

(172 citation statements)

References 142 publications

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“…In addition to their osmotic activity, bile acids promote canalicular secretion of phospholipids and cholesterol for formation of mixed biliary micelles [9]. Canalicular excretion of reduced glutathione and bicarbonate accounts for the major components of the ''bile acid-independent" fraction of bile flow [10]. ''Canalicular bile" is further modified by secretory and absorptive processes as it passes along bile ductules and ducts which secrete mainly bicarbonate (''ductal bile") [4,11,12].…”

Section: Principal Molecular Mechanisms and Regulation Of Bile Formationmentioning

confidence: 99%

New molecular insights into the mechanisms of cholestasis

Wagner

Zollner

Trauner

2009

Journal of Hepatology

237

185

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Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibility and disease progression in acquired cholestatic disorders. Cholestasis is associated with complex transcriptional and post-transcriptional alterations of hepatobiliary transporters and enzymes participating in bile formation. Ligand-activated nuclear receptors for bile acids and other biliary compounds play a key role in the regulation of genes required for bile formation. Pharmacological interventions in cholestasis may aim at modulating such novel regulatory pathways. This review will summarize the principles of molecular alterations in cholestasis and will give an overview of potential clinical implications.

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Section: Principal Molecular Mechanisms and Regulation Of Bile Formationmentioning

confidence: 99%

New molecular insights into the mechanisms of cholestasis

Wagner

Zollner

Trauner

2009

Journal of Hepatology

237

185

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“…Therefore, the hepatic extraction and excretion rates were determined in the absence and presence of loxiglumide in order to characterize the mechanism responsible for the inhibition of hepatic CCK uptake by the specific CCK receptor antagonist. Transport of bile acids in the liver involves three major mechanisms [25]: (1) uptake via multispecific, sodium-dependent transport system [1,7,13,34], (2) intracellular transport via interaction with cytoplasmic proteins [4], and (3) secretion at the canalicular membrane into bile via a sodium-independent transport system. The rate-limiting step is the canalicular bile salt secretion.…”

Section: Discussionmentioning

confidence: 99%

Impairment of hepatic transport processes in perfused rat liver by the specific CCK receptor antagonist loxiglumide

et al. 1997

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The specific cholecystokinin (CCK) receptor antagonist loxiglumide has been used in several human and animal studies to investigate the role of CCK in gastrointestinal physiology. In the present study, the interference of this CCK receptor antagonist with hepatic transport processes was characterized in the perfused rat liver. Indocyanine green, an organic dye which is secreted into bile without being metabolized, was taken up in control experiments at a rate of 68.1 +/- 7.7%. The CCK receptor antagonist lowered the extraction to 0.5 +/- 2.6% (P < 0.001). The compound diminished the hepatic extraction of CCK-8 from 90.95 +/- 2.60% to 4.90 +/- 1.95% (P < 0.001) and of gastrin from 22.2 +/- 1.1% to 8.2 +/- 1.9% (P < 0.001). The hepatic extraction of lidocaine, which is metabolized by the cytochrome P450 system, was only slightly altered. For leukotrienes and taurocholate, the rate-limiting step for transport into bile is secretion across the canalicular membrane; the hepatic extraction of leukotriene D4 was markedly diminished by loxiglumide whereas the transport of taurocholate was only slightly inhibited. The present study demonstrates that the specific CCK receptor antagonist loxiglumide diminished the hepatic extraction of various substances, including peptides and organic anions. It did not interfere with the cytochrome P450 system. The pronounced reduction of hepatic uptake of indocyanine green and leukotriene may be due to an interference with the transport system of these substances in the liver.

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“…At lower doses, alcohol can act as a stimulant, inducing feelings of euphoria and talkativeness, but drinking too much alcohol at one session can lead to drowsiness, respiratory depression [93]. As well as its acute and potentially lethal sedative effect at high doses, alcohol has effects on every organ in the body, and these effects depend on the blood alcohol concentration (BAC) over time [76,77].…”

Section: Diet-induced Hepatotoxicitymentioning

confidence: 99%

“…The liver is composed of two types of epithelial cells, which are hepatocytes and cholangiocytes (i.e., biliary epithelial cells) [92]. Cholangiocytes line the intra-and extra-hepatic bile ducts of the biliary system, cholangiocytes modify the composition of bile that is secreted at the canalicular membranes of hepatocytes as it flows through the biliary system [93]. Biliary obstruction causes cholestatic injury to the liver, including hepatocellular necrosis and apoptosis via free radical generation [94].…”

Section: Bile Ducts Ligationmentioning

confidence: 99%