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Furosemide — Pharmacology and cellular mode of action

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Summary

Furosemide produces in man a renal loss of sodium, chloride, calcium, magnesium and to a small extent potassium, its actions therefore are not ion specific. Furosemide has been shown to inhibit active chloride reabsorption in the thick ascending limb of Henle's loop in rabbits and this appears to be its major pharmacological effect.

Furosemide has the following biochemical actions on the isolated toad bladder, a membrane exhibiting vasopressin stimulable active sodium transport, an effect mediated by cAMP. It displaces cyclic AMP from specific cyclic AMP binding protein, it also inhibits the phosphorylation of histones by a cAMP dependent protein kinase, these effects require 6×10−4 M frusemide. Furosemide has no effect on resting or hormone stimulated levels of cAMP in toad bladder cells, though ethacrynic acid reduces both. Ethacrynic acid has no effect on the cAMP dependent mechanisms affected by furosemide.

From these results we conclude that the biochemical link between furosemide and ethacrynic acid is their effects on cAMP mechanisms. We know renal calcium handling mechanisms are cAMP dependent, is cAMP implicated in renal handling of chloride and sodium?

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Authors and Affiliations

  1. Department of Pharmacology, University of Bristol, Bristol, UK

    D. R. Ferguson & B. R. Twite

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  1. D. R. Ferguson
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  2. B. R. Twite
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Ferguson, D.R., Twite, B.R. Furosemide — Pharmacology and cellular mode of action. Naunyn-Schmiedeberg's Arch. Pharmacol. 281, 295–300 (1974). https://doi.org/10.1007/BF00500598

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  • DOI: https://doi.org/10.1007/BF00500598

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