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Effects of Ethacrynic Acid upon Membrane ATPase of Dog Kidney in Vivo and in Vitro
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1972
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Ethacrynic AcidExperimental PharmacologyDog KidneyPharmacokineticsPre-clinical PharmacologyMolecular PharmacologyRenal FunctionBioanalysisContralateral KidneysChronic Kidney DiseaseRenal PharmacologyMembrane AtpaseAtpase ReceptorBiochemistrySodium HomeostasisRenal PathophysiologyPharmacologyPotassium HomeostasisUrologyPhysiologyDog KidneysClinical PharmacologyMedicineNephrologyKidney ResearchDrug Analysis
Na-K-Mg-dependent ATPase preparations isolated from dog kidneys undergoing ipsilateral saluretic response to ethacrynic acid contained quite reproducible levels of drug-derived radoactivity (ca. 5 × 10-10 moles/mg of protein), and were significantly inhibited relative to contralateral kidneys removed immediately prior to dosage. Inhibition was specifically of the Na-K-dependent fraction of total ATPase, and was essentially irreversible by soluble thiol, and upon dilution and prolonged incubation. With respect to the final assay system, I50 in microsomes labeled in vivo was 7.6 × 10-8M; respective values following introduction of drug at various stages of isolation ranged from 50- to 4500-fold higher, emphasizing the ability of the intact organ to concentrate drug disproportionately at ATPase receptor(s).