Concentrative uptake of digoxin by slices of chicken renal cortex

Wernke, Michael J.; Cacini, William

doi:10.1016/0006-2952(90)90142-8

Biochemical Pharmacology

1990

DOI: 10.1016/0006-2952(90)90142-8

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Concentrative uptake of digoxin by slices of chicken renal cortex

Michael J. Wernke

William Cacini

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Cited by 3 publications

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“…accumulation, and subcellular distribution of [3H]ADR by incubated :slices of mouse ventricles. Similarly designed studies have been reported previously in studying the uptake of digoxin by renal cortex slices (Wernke and Cacini, 1990).…”

mentioning

confidence: 58%

In Vitro Uptake and Subcellular Distribution of the Cardiotoxin [3H]Adriamycin in Mouse Ventricle Slices

Hollinger

Giri

1996

Journal of the American College of Toxicology

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Adriamycin (ADR) is a drug with relatively selective cardiotoxicity. The present study was designed to investigate its distribution into heart subcellular components and correlate such distribution with proposed loci of cardiotoxicity. Uptake of [3H]ADR by mouse ventricular slices was linear for 30 min and plateaued thereafter. The uptake was temperature dependent, being linear from 0° to 45°C. Uptake was also linear over an ADR concentration range of 0.59–8.85 times 10-4 M and increased with wet weight of tissue (25–110 mg). Preincubation with metabolic inhibitors (10-4 M; iodoacetamide and 2,4-dinitrophenol) or 100% N2 failed to affect uptake. Subcellular distribution studies demonstrated preferential localization in nuclei, mitochondria, microsome, and soluble fractions (dpm/μmg protein) in diminishing order, respectively. Therefore, the uptake of ADR by mouse ventricular slices does not involve an energy-dependent transport process and its subcellular localization corresponds with proposed loci of cardiotoxicity.

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mentioning

confidence: 58%

In Vitro Uptake and Subcellular Distribution of the Cardiotoxin [3H]Adriamycin in Mouse Ventricle Slices

Hollinger

Giri

1996

Journal of the American College of Toxicology

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Predicting the physiological response of Tivela stultorum hearts with digoxin from cardiac parameters using artificial neural networks

et al. 2017

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Multi-layer perceptron artificial neural networks (MLP-ANNs) were used to predict the concentration of digoxin needed to obtain a cardio-activity of specific biophysical parameters in Tivela stultorum hearts. The inputs of the neural networks were the minimum and maximum values of heart contraction force, the time of ventricular filling, the volume used for dilution, heart rate and weight, volume, length and width of the heart, while the output was the digoxin concentration in dilution necessary to obtain a desired physiological response. ANNs were trained, validated and tested with the dataset of the in vivo experiment results. To select the optimal network, predictions for all the dataset for each configuration of ANNs were made, a maximum 5% relative error for the digoxin concentration was set and the diagnostic accuracy of the predictions made was evaluated. The double-layer perceptron had a barely higher performance than the single-layer perceptron; therefore, both had a good predictive ability. The double-layer perceptron was able to obtain the most accurate predictions of digoxin concentration required in the hearts of T. stultorum using MLP-ANNs.

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Energy-dependent transport of digoxin across renal tubular cell monolayers (LLC-PK1)

Itô¹,

Koren²,

Harper³

et al. 1993

Can. J. Physiol. Pharmacol.

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Digoxin secretory transport across renal tubular cell monolayers (LLC-PK1) grown on permeable filters was characterized. Metabolic inhibitors reduced total and specific basolateral to apical (B-A) flux of digoxin and conversely increased the apical to basolateral (A-B) flux. The specific transport of digoxin from the basolateral to the apical compartment was saturable, with a maximum velocity of transport of 184.5 +/- 38.0 pmol.cm-2.h-1 and a Michaelis-Menten constant (Km) of 14.1 +/- 1.6 microM. In addition, B-A flux of digoxin resulted in accumulation of digoxin in the apical compartment against the concentration gradient. P-Glycoprotein inhibitors such as quinidine, verapamil, vincristine, and cyclosporine increased the net A-B flux and inhibited the total B-A flux without affecting the nonspecific flux significantly. Tetraethylammonium, a prototype substrate for an organic cation transport system, had no such effect. Our results suggest that digoxin undergoes transepithelial secretion by an energy-dependent, carrier-mediated process in renal tubules, a process that seems to be distinct from the tetraethylammonium transport system.

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Concentrative uptake of digoxin by slices of chicken renal cortex

Cited by 3 publications

References 15 publications

In Vitro Uptake and Subcellular Distribution of the Cardiotoxin [3H]Adriamycin in Mouse Ventricle Slices

In Vitro Uptake and Subcellular Distribution of the Cardiotoxin [3H]Adriamycin in Mouse Ventricle Slices

Predicting the physiological response of Tivela stultorum hearts with digoxin from cardiac parameters using artificial neural networks

Energy-dependent transport of digoxin across renal tubular cell monolayers (LLC-PK1)

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