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. 1977 Dec;61(4):657–667. doi: 10.1111/j.1476-5381.1977.tb07559.x

Diuretics and the renal adenylate cyclase system

JK Dawborn, S Macneil, TJ Martin
PMCID: PMC1668057  PMID: 202362

Abstract

1 The relationship between the diuretic effectiveness and the effect on the renal adenylate cyclase of three diuretics, acetazolamide, frusemide and ethacrynic acid, was examined. The hypothesis that acetazolamide and parathyroid hormone (PTH), inhibit renal carbonic anhydrase by a cyclic adenosine 3′,5′-monophosphate (cyclic AMP)-dependent mechanism was also tested.

2 In vitro, acetazolamide, frusemide and ethacrynic acid at high concentrations (10-3M) all produced some inhibition of basal and stimulated rat kidney plasma membrane adenylate cyclase. The effect of acetazolamide was much less than that of frusemide and ethacrynic acid. These plasma membrane effects were reproduced in studies of cyclic AMP formation in isolated kidney tubules of rats.

3 Intravenous injections of acetazolamide did not change the total cyclic AMP content of the kidneys of rats killed by microwave irradiation.

4 Acetazolamide produced a diuresis in the rat and a slight inhibition of the antidiuretic effect of Pitressin. Frusemide produced a diuresis and greatly reduced the antidiuretic response to Pitressin. Ethacrynic acid was ineffective as a diuretic in the rat and actually enhanced the antidiuretic response to Pitressin.

5 In investigating the possible influence of diuretics and PTH on the activity and state of phosphorylation of carbonic anhydrase it was found that: there was no correlation between the ability of diuretics to inhibit carbonic anhydrase activity and to inhibit carbonic anhydrase phosphorylation; neither PTH nor cyclic AMP (in the presence of adenosine triphosphate, Mg2+, K+ and incubation at 37°C) inhibited rat cortex homogenate carbonic anhydrase activity.

6 It seems unlikely that any of the tested diuretics exerts its pharmacological effect by means of changes in kidney cyclic AMP metabolism.

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Selected References

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  1. Abramow M. Effects of ethacrynic acid on the isolated collecting tubule. J Clin Invest. 1974 Mar;53(3):796–804. doi: 10.1172/JCI107618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes L. D., Hui Y. S., Dousa T. P. Interaction of ethacrynic acid and cysteine with renal medullary adenylate cyclase. Life Sci. 1975 Jan 15;16(2):255–262. doi: 10.1016/0024-3205(75)90023-5. [DOI] [PubMed] [Google Scholar]
  3. Beck N., Kim K. S., Davis B. B. Effect of chlorpropamide on cyclic AMP in rat renal medulla. Endocrinology. 1974 Sep;95(3):771–775. doi: 10.1210/endo-95-3-771. [DOI] [PubMed] [Google Scholar]
  4. Beck N., Kim K. S., Wolak M., Davis B. B. Inhibition of carbonic anhydrase by parathyroid hormone and cyclic AMP in rat renal cortex in vitro. J Clin Invest. 1975 Jan;55(1):149–156. doi: 10.1172/JCI107905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown B. L., Albano J. D., Ekins R. P., Sgherzi A. M. A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate. Biochem J. 1971 Feb;121(3):561–562. doi: 10.1042/bj1210561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CZACZKES J. W., KLEEMAN C. R., KOENIG M. PHYSIOLOGIC STUDIES OF ANTIDIURETIC HORMONE BY ITS DIRECT MEASUREMENT IN HUMAN PLASMA. J Clin Invest. 1964 Aug;43:1625–1640. doi: 10.1172/JCI105038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ebel H. Effect of diuretics on renal NaK-ATPase and adenyl cyclase. Naunyn Schmiedebergs Arch Pharmacol. 1974;281(3):301–314. doi: 10.1007/BF00500599. [DOI] [PubMed] [Google Scholar]
  8. Ebel H., Sharp G. W. Renal adenylate cyclase-effects of diuretics. Eur J Pharmacol. 1975 Dec;34(2):273–281. doi: 10.1016/0014-2999(75)90252-6. [DOI] [PubMed] [Google Scholar]
  9. Engle J. E., Steele T. H. Renal phosphate reabsorption in the rat: effect of inhibitors. Kidney Int. 1975 Aug;8(2):98–104. doi: 10.1038/ki.1975.85. [DOI] [PubMed] [Google Scholar]
  10. Ferguson D. R., Twite B. R. Inhibition by diuretics of cyclic 3',5'-AMP-dependent protein kinase from toad bladder epithelium. Br J Pharmacol. 1973 Oct;49(2):288–292. doi: 10.1111/j.1476-5381.1973.tb08374.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ferrendelli J. A., Johnson E. M., Jr, Chang M., Needleman P. Inhibition of brain adenylate cyclase by ethacrynic acid and dithiobisnitrobenzoic acid. Biochem Pharmacol. 1973 Dec 1;22(23):3133–3136. doi: 10.1016/0006-2952(73)90206-2. [DOI] [PubMed] [Google Scholar]
  12. Gardner J. D., Klaeveman H. L., Bilezikian J. P., Aurbach G. D. Effect of beta-adrenergic catecholamines on sodium transport in turkey erythrocytes. J Biol Chem. 1973 Aug 25;248(16):5590–5597. [PubMed] [Google Scholar]
  13. Garg L. C. Failure of parathyroid hormone and cyclic AMP to inhibit renal carbonic anhydrase. Pflugers Arch. 1976 Nov 30;367(1):103–104. doi: 10.1007/BF00583662. [DOI] [PubMed] [Google Scholar]
  14. Harris C. A., Jenner F. A. Some aspects of the inhibition of the action of antidiuretic hormone by lithium ions in the rat kidney and bladder of the toad Bufo marinus. Br J Pharmacol. 1972 Feb;44(2):223–232. [PMC free article] [PubMed] [Google Scholar]
  15. Hunt N. H., Martin T. J., Michelangeli V. P., Eisman J. A. Effect of guanyl nucleotides on parathyroid hormone-responsive adenylate cyclase in chick kidney. J Endocrinol. 1976 Jun;69(3):401–412. [PubMed] [Google Scholar]
  16. Jacobson H. R., Kokko J. P. Diuretics: sites and mechanisms of action. Annu Rev Pharmacol Toxicol. 1976;16:201–214. doi: 10.1146/annurev.pa.16.040176.001221. [DOI] [PubMed] [Google Scholar]
  17. Jakobs K. H., Schultz K., Schultz G. Hemmung von adenyl-Cyclase-Präparationen aus der Rattenniere durch Calciumionen und verschiedene Diuretica. Naunyn Schmiedebergs Arch Pharmacol. 1972;273(3):248–266. doi: 10.1007/BF00501417. [DOI] [PubMed] [Google Scholar]
  18. KOMORN R., CAFRUNY E. J. EFFECTS OF ETHACRYNIC ACID ON RENAL PROTEIN-BOUND SULFHYDRYL GROUPS. J Pharmacol Exp Ther. 1965 Jun;148:367–372. [PubMed] [Google Scholar]
  19. Knox F. G., Haas J. A., Lechene C. P. Effect of parathyroid hormone on phosphate reabsorption in the presence of acetazolamide. Kidney Int. 1976 Sep;10(3):216–220. doi: 10.1038/ki.1976.100. [DOI] [PubMed] [Google Scholar]
  20. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  21. Larkins R. G., MacAuley S. J., Rapoport A., Martin T. J., Tulloch B. R., Byfield P. G., Matthews E. W., MacIntyre I. Effects of nucleotides, hormones, ions, and 1,25-dihydroxycholecalciferon on 1,25-dihydroxycholecalciferol production in isolated chick renal tubules. Clin Sci Mol Med. 1974 May;46(5):569–582. doi: 10.1042/cs0460569. [DOI] [PubMed] [Google Scholar]
  22. MAREN T. H. A simplified micromethod for the determination of carbonic anhydrase and its inhibitors. J Pharmacol Exp Ther. 1960 Sep;130:26–29. [PubMed] [Google Scholar]
  23. Moseley J. M., Martin T. J., Robinson C. J., Reit B. W., Tregear G. W. Hormone metabolism and response of adenylate cyclase to parathyroid hormone in kidney. Clin Exp Pharmacol Physiol. 1975 Nov-Dec;2(6):549–557. doi: 10.1111/j.1440-1681.1975.tb01860.x. [DOI] [PubMed] [Google Scholar]
  24. Nahorski S. R., Hunt N. H., Rogers K. J., Jones P., Martin T. J. Studies in vivo on the effects of parathyroid hormone upon kidney cyclic adenosine 3',5'-monophosphate content using rapid tissue fixation by microwave irradiation. Horm Metab Res. 1976 Jul;8(4):311–316. doi: 10.1055/s-0028-1093623. [DOI] [PubMed] [Google Scholar]
  25. Narumi S., Miyamoto E. Activation and phosphorylation of carbonic anhydrase by adenosine 3',5'-monophosphate-dependent protein kinases. Biochim Biophys Acta. 1974 May 20;350(1):215–224. doi: 10.1016/0005-2744(74)90219-8. [DOI] [PubMed] [Google Scholar]
  26. Orloff J., Handler J. The role of adenosine 3',5'-phosphate in the action of antidiuretic hormone. Am J Med. 1967 May;42(5):757–768. doi: 10.1016/0002-9343(67)90093-9. [DOI] [PubMed] [Google Scholar]
  27. Rodriguez H. J., Walls J., Yates J., Klahr S. Effects of acetazolamide on the urinary excretion of cyclic AMP and on the activity of renal adenyl cyclase. J Clin Invest. 1974 Jan;53(1):122–130. doi: 10.1172/JCI107529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. WOODFORD V. R., LEEGWATER N., DRANCE S. M. A comparative study of some carbonic anhydrase inhibitors. Can J Biochem Physiol. 1961 Feb;39:287–295. doi: 10.1139/o61-027. [DOI] [PubMed] [Google Scholar]

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