Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Nov;54(5):1049–1055. doi: 10.1172/JCI107848

Pathogenic Role of Cyclic AMP in the Impairment of Urinary Concentrating Ability in Acute Hypercalcemia

Nama Beck 1, Harbans Singh 1, Sarah W Reed 1, H V Murdaugh 1, Bernard B Davis 1
PMCID: PMC301652  PMID: 4371361

Abstract

A possible association between the impairment of urinary concentrating ability and an impairment of the vasopressin-dependent cyclic AMP system in hypercalcemia was investigated in rat kidneys both in vivo and in vitro. The increases of urinary osmolality and negative free water clearance and the increase of urinary cyclic AMP excretion by vasopressin injection were significantly less in the hypercalcemic rats than in the control rats. The increase of cyclic AMP concentration by vasopressin in renal medullary tissue was significantly less in the slices obtained from the hypercalcem'c rats than in those obtained from the control rats. The activation of adenylate cyclase by vasopressin was significantly less in the group with an increased concentration of calcium in media than the control group, but phosphodiesterase activity was not affected by calcium concentration in the media. These data suggest that the impaired urinary concentrating ability in hypercalcemic kidneys is due at least in part to the direct inhibitory effect of calcium on the vasopressin-dependent cyclic AMP system at the level of adenylate cyclase in renal medulla.

Full text

PDF
1049

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agus Z. S., Puschett J. B., Senesky D., Goldberg M. Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog. J Clin Invest. 1971 Mar;50(3):617–626. doi: 10.1172/JCI106532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Argy W. P., Jr, Handler J. S., Orloff J. Ca++ and Mg++ effects on toad bladder response to cyclic AMP, theophylline, and ADH analogues. Am J Physiol. 1967 Sep;213(3):803–808. doi: 10.1152/ajplegacy.1967.213.3.803. [DOI] [PubMed] [Google Scholar]
  3. BECK D., LEVITIN H., EPSTEIN F. H. Effect of intravenous infusions of calcium on renal concentrating ability. Am J Physiol. 1959 Nov;197:1118–1120. doi: 10.1152/ajplegacy.1959.197.5.1118. [DOI] [PubMed] [Google Scholar]
  4. Beck N. P., Kaneko T., Zor U., Field J. B., Davis B. B. Effects of vasopressin and prostaglandin E 1 on the adenyl cyclase-cyclic 3',5'-adenosine monophosphate system of the renal medulla of the rat. J Clin Invest. 1971 Dec;50(12):2461–2465. doi: 10.1172/JCI106746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beck N. P., Reed S. W., Murdaugh H. V., Davis B. B. Effects of catecholamines and their interaction with other hormones on cyclic 3',5'-adenosine monophosphate of the kidney. J Clin Invest. 1972 Apr;51(4):939–944. doi: 10.1172/JCI106888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beck N., Singh H., Reed S. W., Davis B. B. Direct inhibitory effect of hypercalcemia on renal actions of parathyroid hormone. J Clin Invest. 1974 Mar;53(3):717–725. doi: 10.1172/JCI107610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Broadus A. E., Kaminsky N. I., Northcutt R. C., Hardman J. G., Sutherland E. W., Liddle G. W. Effects of glucagon on adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in human plasma and urine. J Clin Invest. 1970 Dec;49(12):2237–2245. doi: 10.1172/JCI106442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CARONE F. A., EPSTEIN F. H., BECK D., LEVITIN The effects upon the kidney of transienthypercalcemia induced by parathyroid extract. Am J Pathol. 1960 Jan;36:77–103. [PMC free article] [PubMed] [Google Scholar]
  9. Chase L. R., Aurbach G. D. Parathyroid function and the renal excretion of 3'5'-adenylic acid. Proc Natl Acad Sci U S A. 1967 Aug;58(2):518–525. doi: 10.1073/pnas.58.2.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chase L. R., Aurbach G. D. Renal adenyl cyclase: anatomically separate sites for parathyroid hormone and vasopressin. Science. 1968 Feb 2;159(3814):545–547. doi: 10.1126/science.159.3814.545. [DOI] [PubMed] [Google Scholar]
  11. Cheung W. Y. Properties of cyclic 3',5'-nucleotide phosphodiesterase from rat brain. Biochemistry. 1967 Apr;6(4):1079–1087. doi: 10.1021/bi00856a017. [DOI] [PubMed] [Google Scholar]
  12. GILL J. R., Jr, BARTTER F. C. On the impairment of renal concentrating ability in prolonged hypercalcemia and hypercalciuria in man. J Clin Invest. 1961 Apr;40:716–722. doi: 10.1172/JCI104305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grantham J. J., Burg M. B. Effect of vasopressin and cyclic AMP on permeability of isolated collecting tubules. Am J Physiol. 1966 Jul;211(1):255–259. doi: 10.1152/ajplegacy.1966.211.1.255. [DOI] [PubMed] [Google Scholar]
  15. Handler J. S., Butcher R. W., Sutherland E. W., Orloff J. The effect of vasopressin and of theophylline on the concentration of adenosine 3',5'-phosphate in the urinary bladder of the toad. J Biol Chem. 1965 Nov;240(11):4524–4526. [PubMed] [Google Scholar]
  16. Kakiuchi S., Yamazaki R. Calcium dependent phosphodiesterase activity and its activating factor (PAF) from brain studies on cyclic 3',5'-nucleotide phosphodiesterase (3). Biochem Biophys Res Commun. 1970 Dec 9;41(5):1104–1110. doi: 10.1016/0006-291x(70)90199-3. [DOI] [PubMed] [Google Scholar]
  17. Kaminsky N. I., Broadus A. E., Hardman J. G., Jones D. J., Jr, Ball J. H., Sutherland E. W., Liddle G. W. Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2387–2395. doi: 10.1172/JCI106458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Loten E. G., Sneyd J. G. An effect of insulin on adipose-tissue adenosine 3':5'-cyclic monophosphate phosphodiesterase. Biochem J. 1970 Nov;120(1):187–193. doi: 10.1042/bj1200187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. MANITIUS A., LEVITIN H., BECK D., EPSTEIN F. H. On the mechanism of impairment of renal concentrating ability in hypercalcemia. J Clin Invest. 1960 Apr;39:693–697. doi: 10.1172/JCI104085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Marcus R., Aurbach G. D. Bioassay of parathyroid hormone in vitro with a stable preparation of adenyl cyclase from rat kidney. Endocrinology. 1969 Nov;85(5):801–810. doi: 10.1210/endo-85-5-801. [DOI] [PubMed] [Google Scholar]
  22. Marumo F., Edelman I. S. Effects of Ca++ and prostaglandin E1 on vasopressin activation of renal adenyl cyclase. J Clin Invest. 1971 Aug;50(8):1613–1620. doi: 10.1172/JCI106649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nagata N., Rasmussen H. Parathyroid hormone, 3'5' AMP, Ca++, and renal gluconeogenesis. Proc Natl Acad Sci U S A. 1970 Feb;65(2):368–374. doi: 10.1073/pnas.65.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. ORLOFF J., HANDLER J. S. THE CELLULAR MODE OF ACTION OF ANTIDIURETIC HORMONE. Am J Med. 1964 May;36:686–697. doi: 10.1016/0002-9343(64)90180-9. [DOI] [PubMed] [Google Scholar]
  25. ORLOFF J., HANDLER J. S. The similarity of effects of vasopressin, adenosine-3',5'-phosphate (cyclic AMP) and theophylline on the toad bladder. J Clin Invest. 1962 Apr;41:702–709. doi: 10.1172/JCI104528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. PETERSEN M. J., EDELMAN I. S. CALCIUM INHIBITION OF THE ACTION OF VASOPRESSIN ON THE URINARY BLADDER OF THE TOAD. J Clin Invest. 1964 Apr;43:583–594. doi: 10.1172/JCI104943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Puschett J. B., Moranz J., Kurnick W. S. Evidence for a direct action of cholecalciferol and 25-hydroxycholecalciferol on the renal transport of phosphate, sodium, and calcium. J Clin Invest. 1972 Feb;51(2):373–385. doi: 10.1172/JCI106823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Suki W. N., Eknoyan G., Rector F. C., Jr, Seldin D. W. The renal diluting and concentrating mechanism in hypercalcemia. Nephron. 1969;6(1):50–61. doi: 10.1159/000179715. [DOI] [PubMed] [Google Scholar]
  29. Thompson W. J., Appleman M. M. Multiple cyclic nucleotide phosphodiesterase activities from rat brain. Biochemistry. 1971 Jan 19;10(2):311–316. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES