Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver

Gerloff, Thomas; Geier, Andreas; Stieger, Bruno; Hagenbuch, Bruno; Meier, Peter J.; Matern, Siegfried; Gartung, Carsten

doi:10.1016/s0016-5085(99)70291-x

Cited by 93 publications

(72 citation statements)

References 33 publications

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“…After delivery, the expression of Ntcp is increased [36,84]. Finally, in the regenerating rat liver, Ntcp is transiently down regulated both at the mRNA, protein and functional level [64,93,99,331].…”

Section: Pathophysiologymentioning

confidence: 99%

“…Functionally, prolactin treatment of ovarectomized rats leads to an increase of ATP-dependent bile salt transport into canalicular vesicles without a change of the K m value [199]. After partial hepatectomy as a model for the regenerating liver, Bsep expression remains practically unchanged at the mRNA and at the protein level [331] or is mildly upregulated [64,93]. This is paralleled by an unchanged ATP-dependent taurocholate transport into isolated canalicular plasma membrane vesicles from regenerating rat liver [99].…”

Section: Pathophysiologymentioning

confidence: 99%

See 1 more Smart Citation

The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

Stieger

2010

Handbook of Experimental Pharmacology

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245

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Section: Pathophysiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

Stieger

2010

Handbook of Experimental Pharmacology

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245

260

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“…Ischemia and resulting hypoxia is always a consequence of hepatic surgery needed to isolate hepatocytes, regardless of species, and has been described to be critical for the quality of the isolated cells (Richert et al, 2004;Berendsen et al, 2011). Downregulation of drug uptake transporters in hepatocytes has been described to be a result of the time in ischemia and hypoxia as well as liver injury and cholestasis, starting within 30 minutes of liver injury in rat (Gartung et al, 1996;Gerloff et al, 1999;Vos et al, 1999;Donner et al, 2013). The downregulation Fig.…”

mentioning

confidence: 99%

The Impact of Solute Carrier (SLC) Drug Uptake Transporter Loss in Human and Rat Cryopreserved Hepatocytes on Clearance Predictions

et al. 2014

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Cryopreserved hepatocytes are often used as a convenient tool in studies of hepatic drug metabolism and disposition. In this study, the expression and activity of drug transporters in human and rat fresh and cryopreserved hepatocytes was investigated. In human cryopreserved hepatocytes, Western blot analysis indicated that protein expression of the drug uptake transporters [human Na + -taurocholate cotransporting polypeptide (NTCP), human organic anion transporting polypeptides (OATPs), human organic anion transporters, and human organic cation transporters (OCTs)] was considerably reduced compared with liver tissue. In rat cryopreserved cells, the same trend was observed but to a lesser extent. Several rat transporters were reduced as a result of both isolation and cryopreservation procedures. Immunofluorescence showed that a large portion of remaining human OATP1B1 and OATP1B3 transporters were internalized in human cryopreserved hepatocytes. Measuring uptake activity using known substrates of OATPs, OCTs, and NTCP showed decreased activity in cryopreserved as compared with fresh hepatocytes in both species. The reduced uptake in cryopreserved hepatocytes limited the in vitro metabolism of several AstraZeneca compounds. A retrospective analysis of clearance predictions of AstraZeneca compounds suggested systematic lower clearance predicted using metabolic stability data from human cryopreserved hepatocytes compared with human liver microsomes. This observation is consistent with a loss of drug uptake transporters in cryopreserved hepatocytes. In contrast, the predicted metabolic clearance from fresh rat hepatocytes was consistently higher than those predicted from liver microsomes, consistent with retention of uptake transporters. The uptake transporters, which are decreased in cryopreserved hepatocytes, may be rate-limiting for the metabolism of the compounds and thus be one explanation for underpredictions of in vivo metabolic clearance from cryopreserved hepatocytes.

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“…The formation of bile is dependent on the active secretion of bile salts and other biliary constituents into the bile canaliculus by specific bile acid and organic anion transporters [99] . Gerloff et al [100] demonstrated that the expression of two ATP-dependent transporters [bile salt acid pump (Bsep) and multi-organic anion transporter (Mrp2)] was unchanged or slightly increased following partial hepatectomy in rats and this provided a potential mechanism by which the regenerating liver cells maintained or increased bile secretion. The authors in this study also suggested that the down-regulation of certain transporters [sodium-taurocholate cotransporter (Ntcp) and organic anion transporting polypeptides (Oatp1 and Oatp2)] could be a protective mechanism against the potentially hepatotoxic bile salts [100] .…”

Section: Metabolic Demand Of the Livermentioning

confidence: 99%

“…Gerloff et al [100] demonstrated that the expression of two ATP-dependent transporters [bile salt acid pump (Bsep) and multi-organic anion transporter (Mrp2)] was unchanged or slightly increased following partial hepatectomy in rats and this provided a potential mechanism by which the regenerating liver cells maintained or increased bile secretion. The authors in this study also suggested that the down-regulation of certain transporters [sodium-taurocholate cotransporter (Ntcp) and organic anion transporting polypeptides (Oatp1 and Oatp2)] could be a protective mechanism against the potentially hepatotoxic bile salts [100] . The differential regulation of hepatobiliary transporters during the regeneration process are likely to be mediated by cytokines such as TNF-α [101] .…”

Section: Metabolic Demand Of the Livermentioning

confidence: 99%

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

Gomez¹

2007

WJG

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Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemicreperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords "liver", "ischaemic reperfusion", "ischaemic preconditioning", "regeneration", "hepatectomy" and "transplantation". The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growthpromoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation.

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Differential expression of basolateral and canalicular organic anion transporters during regeneration of rat liver

Cited by 93 publications

References 33 publications

The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

The Impact of Solute Carrier (SLC) Drug Uptake Transporter Loss in Human and Rat Cryopreserved Hepatocytes on Clearance Predictions

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

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