Extrapolating In vitro Metabolic Interactions to Isolated Perfused Liver: Predictions of Metabolic Interactions between R-Bufuralol, Bunitrolol, and Debrisoquine

2010 ◽  
Vol 99 (10) ◽  
pp. 4406-4426 ◽  
Author(s):  
Sami Haddad ◽  
Patrick Poulin ◽  
Christoph Funk
Keyword(s):  
Perfused Liver ◽  
Isolated Perfused Liver ◽  
Metabolic Interactions

scholarly journals Effect of thyroid state on cyclic AMP-mediated induction of hepatic phosphoenolpyruvate carboxykinase

1985 ◽  
Vol 226 (1) ◽  
pp. 67-73 ◽  
Author(s):  
W Höppner ◽  
W Süssmuth ◽  
H J Seitz
Keyword(s):  
Cyclic Amp ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Close Correlation ◽  
Perfused Liver ◽  
Thyroid State ◽  
Fed State ◽  
Isolated Perfused Liver ◽  
Translatable Mrna

Hepatic phosphoenolpyruvate carboxykinase (PEPCK) is significantly increased in the hyperthyroid starved rat, and moderately decreased in the hypothyroid starved rat. As tri-iodothyronine by itself has only a small and sustained effect on the induction of this enzyme, as was previously shown in the isolated perfused organ, the effect of hypo- and hyper-thyroidism on the increase in cytosolic PEPCK provoked by dibutyryl cyclic AMP (Bt2cAMP) was investigated in vivo and in the isolated perfused liver. Compared with euthyroid fed controls, in hypothyroid fed rats Bt2cAMP provoked in 2 h only a small increase in translatable mRNA coding for PEPCK. In contrast, in hyperthyroid animals PEPCK mRNA as measured by translation in vitro was already increased in the fed state, and further enhanced by Bt2cAMP injection to values as in euthyroid controls. Under all thyroid states a close correlation between PEPCK mRNA activity and PEPCK synthesis was observed. In the isolated perfused liver from the hyperthyroid fed rat, the increase in PEPCK provoked by Bt2cAMP or Bt2cAMP + isobutylmethylxanthine was considerably enhanced compared with those obtained in livers of hypothyroid rats. Also, adrenaline provoked a stimulated induction of PEPCK in hyperthyroid rats compared with hypothyroid rats. To summarize, our data indicate that the primary action of thyroid hormones on the synthesis of hepatic cytosolic PEPCK is to accelerate the cyclic AMP- or adrenaline-induction of the enzyme, acting primarily at a pretranslational level.

Influence of hepatic taurine concentration on bile acid conjugation with taurine.

1977 ◽  
Vol 232 (1) ◽  
pp. E75 ◽  
Author(s):  
W G Hardison ◽  
J H Proffitt
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Sodium Cholate ◽  
Total Bile Acid ◽  
Perfused Liver ◽  
Taurine Concentration ◽  
Isolated Perfused Liver ◽  
Liver Homogenates

In vitro, addition of taurine to liver homogenates increases the proportion of cholic acid conjugated with taurine. In the present study, the relation between hepatic taurine concentration and the proportion of infused sodium cholate conjugated with taurine was studied in the whole organ. The isolated perfused liver was studied to eliminate possible transfer of taurine to or from the large extrahepatic poosl present in vivo. During cholate infusion, the proportion of taurocholate excreted in bile decreased, and the proportion of glycocholate increased in a complementary fashion. Infusion of taurine with cholate prevented these changes. Hepatic taurine concentration, calculated from measured hepatic taurine concentrations before and at the end of cholate infusion, fell. Fall in proportion of total bile acid excreted as taurocholate was most rapid at low hepatic taurine concentrations between about 1.4 and 0.65 mumol/g liver. Hepatic taurine concentrations is a major determinant of the proportion of bile acid conjugated with taurine.

scholarly journals Metabolic fates of diethylstilboestrol sulphates in the rat

1977 ◽  
Vol 164 (2) ◽  
pp. 423-430 ◽  
Author(s):  
P A Barford ◽  
A H Olavesen ◽  
C G Curtis ◽  
G M Powell
Keyword(s):  
Rat Liver ◽  
Whole Body ◽  
Perfused Liver ◽  
Isolated Perfused Liver

The metabolic fates and modes of excretion of diethylstilboestrol mono[35S]sulphate and diethylstilboestrol di[35S]sulphate were studied in the rat. Both of the esters were desulphated to some extent in vivo. In addition, significant amounts of radioactivity appeared in the bile as diethylstilboestrol mono[35S]sulphate monoglucuronide. The percentage of the dose appearing in bile as the diconjugate was substantially greater in experiments with diethylstilboestrol mono[35S]sulphate than with diethylstilboestrol di[35S]sulphate. Whole-body radioautography and studies with isolated perfused liver confirmed the liver as the major metabolic organ for both esters. When the metabolite diethylstilboestrol mono[35S]sulphate monoglucuronide isolated from the bile was reinjected, it was excreted in the bile unchanged. Studies in vitro demonstrated that both esters were substrates for arylsulphatase C with Km values in the range 52-76 micrometer. The metabolic fates and modes of excretion of the esters are discussed in relation to the enzyme complement of rat liver.

Loperamide inhibits the biliary excretion of irinotecan (CPT-11) in the rat isolated perfused liver

2005 ◽  
Vol 57 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Peter J. Tobin ◽  
Ying Hong ◽  
J. Paul Seale ◽  
Laurent P. Rivory ◽  
Andrew J. McLachlan
Keyword(s):  
Biliary Excretion ◽  
Perfused Liver ◽  
Isolated Perfused Liver

scholarly journals Thyroid hormone differentially augments biliary sterol secretion in the rat. I. The isolated-perfused liver model.

1992 ◽  
Vol 33 (10) ◽  
pp. 1459-1466
Author(s):  
RL Gebhard ◽  
BG Stone ◽  
JP Andreini ◽  
WC Duane ◽  
CD Evans ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Perfused Liver ◽  
Isolated Perfused Liver ◽  
Liver Model
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