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Effect of diuretics on renal NaK-ATPase and adenyl cyclase

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Summary

Contradictory results on the role of NaK-ATPase as the diuretic receptor are reported in the literature. In own experiments the effects of 1 mM ouabain and 0.2 mM ethacrynic acid on fractional sodium reabsorption and oxygen consumption was investigated in an isolated perfused kidney system. NaK-ATPase was measured in basal-lateral membranes of kidney cortex tubular cells. Combination of ouabain and ethacrynic acid resulted in a complete inhibition of fractional sodium reabsorption at only a 46% inhibition of NaK-ATPase activity. The complete inhibition of sodium reabsorption at only a partial inhibition of NaK-ATPase probably is caused by additional metabolic effects of ethacrynic acid. It is suggested that NaK-ATPase is not the only diuretic receptor. — Another enzyme possibly involved in the control of sodium transport and water permeability is the renal adenyl cyclase. 1 mM furosemide and 1 mM ethacrynic acid inhibited the enzyme in homogenates of the kidney cortex and inner medulla, while amiloride was without any effect. In the cortex the furosemide induced inhibition of adenyl cyclase can be reversed by 1 U parathyroid hormone and 0.1 mM isoproterenol. The ethacrynic acid effect on adenyl cyclase was not influenced by isoproterenol. In the inner medulla 1 mU antidiuretic hormone but not isoproterenol antagonized the furosemide inhibition of adenyl cyclase. Antidiuretic hormone and isoproterenol exerted no effect on the ethacrynic acid inhibition of adenyl cyclase. It is suggested that furosemide and ethacrynic acid act at different sites of the adenyl cyclase or at a mixture of adenyl cyclases with different sensitivities.

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  1. Institut für Klinische Physiologie, Klinikum Steglitz, Freie Universität Berlin, Berlin, Germany

    H. Ebel

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This work was supported by grants of the Deutsche Forschungsgemeinschaft.

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Ebel, H. Effect of diuretics on renal NaK-ATPase and adenyl cyclase. Naunyn-Schmiedeberg's Arch. Pharmacol. 281, 301–314 (1974). https://doi.org/10.1007/BF00500599

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