Studies on 14C-imipramine Metabolism in the Isolated Perfused Rat Liver

An analytical procedure for the measurement of 14C-imipramine and its metabolites in liver, bile, and perfusion fluid has been studied using the isolated perfused rat liver technique. The extraction efficiency and specificity have been found to be high (efficiency with liver perfusion, 90–100%; specificities: imipramine, 96.6%; desmethylimipramine, 96.7%; imipramine-N-oxide, 90%). The hydroxylation of imipramine was close to the maximal rate at a substrate concentration of 0.5 × 10−4 M (15 min perfusion). The demethylation reaction reached a maximal rate at an estimated substrate concentration of 1.25 × 10−4 M. The formation of the N-oxide metabolite remained linear at 2 × 10−4 M imipramine. It was found that the half-life of imipramine in the perfusion fluid was not an accurate method of estimating imipramine metabolism as a result of a change in distribution. Exogenous desmethylimipramine inhibited the hydroxylation reaction; inhibition of demethylation required higher concentrations.

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Metabolism of Halothane as a Function of Substrate Concentration in the Isolated Perfused Rat Liver Preparation

Deutsche Pharmakologische Gesellschaft ◽

10.1007/978-3-662-39532-5_86 ◽

1978 ◽

pp. 22-22

Author(s):

I. Rösch ◽

E. Dallmeier

Keyword(s):

Rat Liver ◽

Substrate Concentration ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Liver Preparation

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Synthesis of Coagulation Factors and Factor VIII Related Antigen by the Isolated Perfused Rat Liver

10.1055/s-0039-1680436 ◽

1977 ◽

Author(s):

A. L. Bloom ◽

Eryl Shaw ◽

J. C. Giddings ◽

I. R. Peake

Keyword(s):

Factor Viii ◽

Rat Liver ◽

Coagulation Factor ◽

Coagulation Factors ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Perfusion Fluid ◽

Factor Viii Related Antigen ◽

Synthetic Function ◽

Similar Kinetic

The synthesis of coagulation factors, including procoagulant factor VIII (FVIIIC) and factor VIII related antigen (FVIIIRAG) was studied using the isolated perfused rat liver. The perfusion fluid consisted of rat blood cells suspended in Tyrodes solution containing bovine albumin. Synthetic function was confirmed by the addition of 35S l-methionine to the perfusion medium. Using two dimensional crossed Immunoelectrophoresis and autoradiography progressive incorporation of radioactivity into plasma protein was demonstrated. This was inhibited by cyclohexamide. Coagulation factor assays demonstrated the synthesis of factors II, IX and X and of factors V and VIIIC. Demonstration of synthesis of FVIIIRAG was attempted using an immunoradiometric assay and a cross-reacting rabbit anti-human antiserum. FV and FVIIIRAG synthesis was more clearly demonstrated when the perfusion fluid was depleted of leucocytes and platelets. Addition of Warfarin inhibited the synthesis of factors II, IX and X but not of factors V and VIII. Cyclohexamide completely inhibited synthesis of all coagulation factors but actinomycin acted only after a latent period. No coagulation factor synthesis was demonstrated in the perfusion system without a liver. The results confirmed the functional capacity of the isolated perfused liver for synthesising proteins and the vitamin K dependent factors and demonstrated similar kinetic features for the synthesis of factors V, VIIIC and, possibly, VIIIRAG.

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Effect of Sex, Fasting and Alloxan Diabetes on the Uptake of Neutral Fat by Isolated Perfused Rat Liver

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.195.3.673 ◽

1958 ◽

Vol 195 (3) ◽

pp. 673-677 ◽

Cited By ~ 10

Author(s):

Murray Heimberg ◽

H. C. Meng ◽

C. R. Park

Keyword(s):

Rat Liver ◽

Alloxan Diabetes ◽

Hormonal Control ◽

Female Rats ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Perfusion Fluid ◽

Fat Uptake ◽

Isolated Liver

A method is described for measuring the uptake of neutral fat by the perfused rat liver in vitro. The rate of fat uptake by the isolated liver was influenced by the endocrine balance of the animal at the time the organ was removed. Livers from female rats had a significantly greater rate of fat uptake than livers from males. The rate was markedly increased by fasting and by alloxan diabetes. Insulin reduced the fat uptake of the diabetic liver when the hormone was administered to the animal, but was ineffective when added directly to the perfusion fluid. The results suggest that the rate of uptake of neutral fat by the liver is under direct hormonal control.

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ANTAGONISTIC EFFECTS OF DINITROPHENOL AND CYANIDE ON HEPATIC THYROXINE DEIODINATION

Acta Endocrinologica ◽

10.1530/acta.0.0770122 ◽

1974 ◽

Vol 77 (1) ◽

pp. 122-127

Author(s):

A. P. Hillier

Keyword(s):

Rat Liver ◽

Inhibitory Effect ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Perfusion Fluid ◽

Antagonistic Effects ◽

Subsequent Addition

ABSTRACT Dinitrophenol inhibits the deiodination of thyroxine by the isolated perfused rat liver; the effect is reversible. Subsequent addition of cyanide to the perfusion fluid opposes the inhibitory effect of dinitrophenol and restores the deiodination rate to normal. However, addition of cyanide alone has little effect. Similar results are obtained with triiodothyronine.

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A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657155 ◽

1982 ◽

Vol 47 (02) ◽

pp. 166-172 ◽

Cited By ~ 4

Author(s):

Yoav Sharoni ◽

Maria C Topal ◽

Patricia R Tuttle ◽

Henry Berger

Keyword(s):

Rat Liver ◽

Isoelectric Point ◽

Rat Hepatocytes ◽

Cell Types ◽

Plasminogen Activators ◽

Rat Plasma ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Molecular Weights ◽

Physiological Relevance

SummaryOf the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.

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