The role of nonparenchymal and parenchymal liver cells in the catabolism of extracellular purines

Leser, H. G.; Holstege, Axel; Gerok, W.

doi:10.1002/hep.1840100114

Cited by 12 publications

(5 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…40 Release of purine nucleoside phosphorylase has also been proposed to indicate endothelial cell killing,41 but this enzyme may not be localized exclusively to nonparenchymal cells as originally thought. 42 Reperfusion-induced endothelial cell killing begins after about 8 hours of storage in Euro-Collins solution and becomes maximal after 24 hours ( Fig 5). If stored livers are infused with cold storage solution, rather than with warm physiological buffer, trypan blue labeling of endothelial nuclei is greatly reduced.…”

Section: Reperfusion Injury To Sinusoidal Endothelial Cellsmentioning

confidence: 99%

Reperfusion injury to donor livers stored for transplantation

1995

View full text Add to dashboard Cite

iver transplantation is an accepted therapy for L end-stage liver disease, allowing resumption of a nearly normal life style by adult and pediatric patients and giving good long-term survival. In 1985, about 600 liver transplantations were performed in the United States. In 1990, this number increased to 2,600, and in 1995 more than 3,000 liver transplantations will be performed. Improvements in surgical technique and immunosuppression have contributed to the increased use of liver transplantation, but perhaps the most important factor favoring this expansion is improved donor liver preservation afforded by the University of Wisconsin (W cold storage solution. l-3 With UW solution, liver transplantation surgery no longer requires 24-hour stand-by availability of surgeons, support staffs, and operating facilities. Moreover, the longer preservation times afforded by U W solution permit lengthy back-table procedures to reduce liver size for pediatric cases, where size-matched organs are s~a r c e ,~ and to split livers, so one donor liver can rescue two patients from terminal liver d i~e a s e .~-~

show abstract

Section: Reperfusion Injury To Sinusoidal Endothelial Cellsmentioning

confidence: 99%

Reperfusion injury to donor livers stored for transplantation

1995

View full text Add to dashboard Cite

show abstract

“…[2-14C]uridine (52 Ci/mol) and [8-l4C1adenosine (49.8 Ci/mol) were from Amersham Buchler (Braunschweig, Germany). Purity was more than 98% for each of the isotopes as determined by reversed-phase HPLC (25,30).…”

Section: Animals Chemicals and Isotopesmentioning

confidence: 99%

“…The liver plays an important role in systemic pyrimidine catabolism under in uiuo conditions (23)(24)(25)(26) and eliminates in a single passage most of the uridine (27,281 and adenosine (29,30) in portal vein blood. A rapid permeation of adenosine and uridine across the cell membrane is a prerequisite for their efficient clearance from the sinusoidal blood by nonparenchymal and parenchymal liver cells (30,31). Using the isolatedperfused rat liver, we were able t o demonstrate for the fist time the presence of a sodium-dependent nucleoside transport system of physiological importance in addition t o the facilitated-diffusion transporter in this organ.…”

mentioning

confidence: 99%

Facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver

Holstege

1991

Hepatology

View full text Add to dashboard Cite

In mammalian cells, nucleoside transport usually is mediated by facilitated diffusion. In addition, a Na(+)-dependent, concentrative nucleoside transport system has been detected in several tissues but not the liver. To further clarify hepatic nucleoside transport mechanisms, we measured the uptake of [2-14C]uridine (2 to 100 mumol/L) and of [8-14C]adenosine (10 to 75 mumol/L) by the isolated perfused rat liver in the presence or absence of extracellular sodium or specific inhibitors of facilitated nucleoside diffusion. Uridine transport and metabolism were monitored by the release of labeled catabolites including 14CO2, which indicated complete degradation of the pyrimidine. Adenosine, uridine and uridine catabolites were measured in the effluent perfusate by reversed-phase high-performance liquid chromatography and a radioactivity flow monitor. The existence of a Na(+)-dependent nucleoside transport system could be inferred from the following observations: (a) Sodium depletion caused a strong inhibition of nucleoside transport reflected by an up to threefold and 15-fold increase in extracellular uridine and adenosine, respectively. The sodium-dependent transport of uridine was saturated when the influent uridine concentration was raised beyond 20 mumol/L. No such saturation was observed for much higher concentrations of adenosine used (10 to 75 mumol/L). (b) Na(+)-free perfusion resulted in a strong suppression of the release of uridine catabolites by the liver. Complete uridine breakdown was depressed to 7% of the amount of 14CO2 released in the presence of sodium and at influent uridine concentrations below 20 mumol/L. (c) Inhibition of uridine (10 mumol/L) transport and degradation was observed after coperfusion with adenosine, deoxyadenosine, guanosine and deoxyguanosine.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…Two cDNAs-cNT1, involved in Na ϩ -dependent pyrimidine transport (N2 type), and sodium purine nucleoside transporter (SPNT), involved in Na ϩ -dependent purine uptake (N1 type)-have recently been cloned. 24,25 Although it has long been known that nucleosides are concentrated in liver, 26 that perfused labeled uridine is efficiently extracted from the afferent blood, 27 and that parenchymal and nonparenchymal liver cells show metabolic cooperation in degrading extracellular nucleosides, 28 the mechanisms of nucleoside uptake into hepatocytes were not studied in detail until this decade. Holstege et al, 29 using the isolated perfused rat liver model, reported indirect evidence of facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver.…”

mentioning

confidence: 99%

Differential Expression and Regulation of Nucleoside Transport Systems in Rat Liver Parenchymal and Hepatoma Cells

et al. 1998

View full text Add to dashboard Cite

Primary cultures of rat-liver parenchymal cells show carrier-mediated nucleoside uptake by a mechanism that mainly involves concentrative, Na ؉ -dependent transport activity. In contrast, the hepatoma cell line FAO shows high nucleoside transport activity, although it is mostly accounted for by Na ؉ -independent transport processes. This is associated with a low amount of sodium purine nucleoside transporter (SPNT) mRNA. SPNT encodes a purinepreferring transporter expressed in liver parenchymal cells. To analyze whether SPNT expression is modulated during cell proliferation, SPNT mRNA levels were determined in the early phase of liver growth after partial hepatectomy and in synchronized FAO cells that had been induced to proliferate. SPNT mRNA amounts increased as early as 2 hours after partial hepatectomy. FAO cells induced to proliferate after serum refeeding show an increase in SPNT mRNA levels, which is followed by an increase in Na ؉ -dependent nucleoside uptake and occurs before the peak of 3 H-thymidine incorporation into DNA. FAO cells also express significant equilibrative nucleoside transport activity, which may be accounted for by the expression of the nitrobenzylthioinosine (NBTI)-sensitive and -insensitive isoforms, rat equilibrative nucleoside transporter 1 (rENT1) and rENT2, respectively. Interestingly, rENT2 mRNA levels follow a similar pattern to that described for SPNT when FAO cells are induced to proliferate, whereas rENT1 appears to be constitutively expressed. Liver parenchymal cells show low and negligible mRNA levels for rENT1 and rENT2 transporters, respectively, although most of the equilibrative transport activity found in hepatocytes is NBTI-resistant. It is concluded that: 1) SPNT expression is regulated both in vivo and in vitro in a way that appears to be dependent on cell cycle progression; 2) SPNT expression may be a feature of differentiated hepatocytes; and 3) equilibrative transporters are differentially regulated, rENT2 expression being cell cycle-dependent. This is consistent with its putative role as a growth factor-induced delayed early response gene. (HEPATOLOGY 1998;28:1504-1511.)Nucleosides and nucleoside analogues have a wide range of potent physiological and pharmacological properties. Purines, essentially adenosine, play a multifactorial role in liver physiology by modulating key metabolic pathways of the hepatocyte 1-5 and influencing, among other functions, hepatic arterial pressure-flow autoregulation, 6 vasodilation, 7 and superoxide anion generation. 8

show abstract

The role of nonparenchymal and parenchymal liver cells in the catabolism of extracellular purines

Cited by 12 publications

References 51 publications

Reperfusion injury to donor livers stored for transplantation

Reperfusion injury to donor livers stored for transplantation

Facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver

Differential Expression and Regulation of Nucleoside Transport Systems in Rat Liver Parenchymal and Hepatoma Cells

Contact Info

Product

Resources

About