Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Mar;53(3):717–725. doi: 10.1172/JCI107610

Direct Inhibitory Effect of Hypercalcemia on Renal Actions of Parathyroid Hormone

Nama Beck 1, Harbans Singh 1, Sarah W Reed 1, Bernard B Davis 1
PMCID: PMC333052  PMID: 4359938

Abstract

The effects of calcium on the renal actions of parathyroid hormone (PTH) were studied in vivo and in vitro. In parathyroidectomized rats, variable levels of blood calcium concentration were induced by intravenous infusion of calcium. The renal responses to the injected PTH, i.e. phosphate and cyclic AMP excretion, were compared in these animals. After PTH injection, the increases of both phosphate and cyclic AMP excretion were less in the calcium-infused animals than in the control group without calcium infusion. There was an inverse correlation between the renal responses to PTH and plasma calcium concentration of 4.2-13.5 mg/100 ml. But calcium had no effect on phosphate excretion induced by infusion of dibutyryl cyclic AMP. In the in vitro experiments, the increase of cyclic AMP concentration in response to PTH was less in renal cortical slices taken from the calcium-infused animals than in ones from the control group without calcium infusion. Calcium also inhibited the activation of renal cortical adenylate cyclase in response to PTH, but calcium had no effect on phosphodiesterase. The data indicate that calcium directly inhibits renal actions of PTH both in vivo and in vitro. Such inhibitory mechanism is probably at or before the step of PTH-dependent cyclic AMP generation in the kidney.

Full text

PDF
720

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. Andreucci V. E., Herrera-Acosta J., Rector F. C., Jr, Seldin D. W. Measurement of single-nephron glomerular filtration rate by micropuncture: analysis of error. Am J Physiol. 1971 Dec;221(6):1551–1559. doi: 10.1152/ajplegacy.1971.221.6.1551. [DOI] [PubMed] [Google Scholar]
  3. Aurbach G. D., Chase L. R. Cyclic 3',5'-adenylic acid in bone and the mechanism of action of parathyroid hormone. Fed Proc. 1970 May-Jun;29(3):1179–1182. [PubMed] [Google Scholar]
  4. Aurbach G. D., Houston B. A. Determination of 3',5'-adenosine monophosphate with a method based on a radioactive phosphate exchange reaction. J Biol Chem. 1968 Nov 25;243(22):5935–5940. [PubMed] [Google Scholar]
  5. Beck N. P., DeRubertis F. R., Michelis M. F., Fusco R. D., Field J. B., Davis B. B. Effect of prostaglandin E 1 on certain renal actions of parathyroid hormone. J Clin Invest. 1972 Sep;51(9):2352–2358. doi: 10.1172/JCI107047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Bradham L. S., Holt D. A., Sims M. The effect of Ca2+ on the adenyl cyclase of calf brain. Biochim Biophys Acta. 1970 Feb 24;201(2):250–260. doi: 10.1016/0304-4165(70)90299-0. [DOI] [PubMed] [Google Scholar]
  8. Burke G. Effects of cations and ouabain on thyroid adenyl cyclase. Biochim Biophys Acta. 1970 Oct 14;220(1):30–41. doi: 10.1016/0005-2744(70)90226-3. [DOI] [PubMed] [Google Scholar]
  9. Butcher R. W. Rose of cyclic AMP in hormone actions. N Engl J Med. 1968 Dec 19;279(25):1378–1384. doi: 10.1056/NEJM196812192792507. [DOI] [PubMed] [Google Scholar]
  10. Bär H. P., Hechter O. Adenyl cyclase and hormone action. 3. Calcium requirement for ACTH stimulation of adenyl cyclase. Biochem Biophys Res Commun. 1969 Jun 6;35(5):681–686. doi: 10.1016/0006-291x(69)90459-8. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Chase L. R., Fedak S. A., Aurbach G. D. Activation of skeletal adenyl cyclase by parathyroid hormone in vitro. Endocrinology. 1969 Apr;84(4):761–768. doi: 10.1210/endo-84-4-761. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Kaneko T., Field J. B. A method for determination of 3',5'-cyclic adenosine monophosphate based on adenosine triphosphate formation. J Lab Clin Med. 1969 Oct;74(4):682–690. [PubMed] [Google Scholar]
  17. Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [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. 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]
  20. Miyamoto E., Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. 3. Purification and properties of adenosine 3',5'-monophosphate-dependent protein kinase from bovine brain. J Biol Chem. 1969 Dec 10;244(23):6395–6402. [PubMed] [Google Scholar]
  21. Moore E. W. Ionized calcium in normal serum, ultrafiltrates, and whole blood determined by ion-exchange electrodes. J Clin Invest. 1970 Feb;49(2):318–334. doi: 10.1172/JCI106241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nagata N., Rasmussen H. Parathyroid hormone and renal cell metabolism. Biochemistry. 1968 Oct;7(10):3728–3733. doi: 10.1021/bi00850a053. [DOI] [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. Shannon J. A., Smith H. W. THE EXCRETION OF INULIN, XYLOSE AND UREA BY NORMAL AND PHLORIZINIZED MAN. J Clin Invest. 1935 Jul;14(4):393–401. doi: 10.1172/JCI100690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sherwood L. M., Mayer G. P., Ramberg C. F., Jr, Kronfeld D. S., Aurbach G. D., Potts J. T., Jr Regulation of parathyroid hormone secretion: proportional control by calcium, lack of effect of phosphate. Endocrinology. 1968 Nov;83(5):1043–1051. doi: 10.1210/endo-83-5-1043. [DOI] [PubMed] [Google Scholar]
  26. Streeto J. M. Renal cortical adenyl cyclase: effect of parathyroid hormone and calcium. Metabolism. 1969 Nov;18(11):968–973. doi: 10.1016/0026-0495(69)90037-7. [DOI] [PubMed] [Google Scholar]
  27. Yamashita K., Bloom G., Field J. B. Effects of ions on thyrotrophin and prostaglandin E stimulation of glucose oxidation and adenyl cyclase-cyclic AMP system in dog thyroid slices. Metabolism. 1971 Oct;20(10):943–953. doi: 10.1016/0026-0495(71)90015-1. [DOI] [PubMed] [Google Scholar]

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

RESOURCES