Pflügers Archiv

, Volume 398, Issue 3, pp 247–252 | Cite as

Blockade of the renal tubular effects of vitamin D by cycloheximide in the rat

  • Meir Brezis
  • Hanna Wald
  • Ruth Shilo
  • Mordecai M. Popovtzer
Article
Received:
Accepted:

Abstract

To further characterize the mechanisms by which 25(OH)vitamin D3 (25(OH)D3) and 1.25(OH)2 vitamin D3 (1,25(OH)2D3) suppress the phosphaturic action of parathyroid hormone (PTH) we have studied the effects of cycloheximide (cyclohex), a protein synthesis inhibitor, on the interaction between PTH and vitamin D metabolites in parathyroidectomized (PTX) rats, both in vivo and in vitro experiments. In clearance studies PTX PTH-infused rats were pretreated with cyclohex 2 h before the administration of vitamin D. In control, PTX PTH-infused rats not pretreated with cyclohex, the administration of 25(OH)D3 and 1,25(OH)2D3 was associated with a fall in fractional excretion of phosphate (CP/CIN) from 0.30±0.05 to 0.16±0.02 and from 0.31±0.05 to 0.13±0.01 (P<0.005) respectively. Cyclohex-pretreated PTX PTH-infused rats failed to respond to both 25(OH)D3 and 1,25(OH)2D3, and CP/CIN, which rose after PTH, remained 0.32±0.05 and 0.29±0.03 respectively. In vitro, both 25(OH)D3 and 1,25(OH)2D3 inhibited the PTH-induced activation of adenylate cyclase in the renal isolated membrane fractions. Pretreatment with cyclohex abolished this effect of vitamin D metabolites. These results show that cyclohex blocks the antiphosphaturic effects of both 25(OH)D3 and 1,25(OH)2D3 but does not alter the response to PTH. These findings are consistent with the possibility that the acute renal action of vitamin D depends on de novo synthesis of protein.

Key words

Vitamin D Parathyroid hormone Cycloheximide Phosphorus 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bordier Ph, Hioco D, Rouguier M (1969) Effects of intravenous vitamin D on bone and phosphate metabolism in osteomalacia. Calc Tiss Res 4:78–83Google Scholar
  2. 2.
    Bronner F (1982) Vitamin D and membrane structure and function. Introduction. Fed Proc 41:60Google Scholar
  3. 3.
    Bronner F, Lipton J, Pansu D, Buckley M, Singh R, Miller A III (1982) Molecular and transport effects 1,25-dihydroxy-vitamin D3 in rat duodenum. Fed Proc 41:61–65Google Scholar
  4. 4.
    Calabresi P, Parks RE Jr (1975) Alkylating agents antimetabolites, hormones and other antiproliferative agents. In: Goodman LS, Gilman AG (eds) The pharmacological basis of therapeutics, 5th edition. MacMillan Inc. New York, p 1287Google Scholar
  5. 5.
    Caskey CT (1973) Inhibitors of protein synthesis. In: Hochster RM, Krates M, Quartel JH (eds) Metabolic inhibitors, vol 4. Academic Press Inc., New York, pp 162–163Google Scholar
  6. 6.
    Chase LR, Aurbach GD (1968) Anatomically separate site for parathyroid hormone and vasopressin. Science 159:545–546Google Scholar
  7. 7.
    Edelman IS (1975) Mechanism of action of steroid hormones. J Steroid Biochem 6:147–159Google Scholar
  8. 8.
    Farese RV, Bidot-Lopez P, Sabir A, Smith JS, Schinbeckler B, Larson R (1980) Parathyroid hormone acutely increases polyphosphoinositides of the rabbit kidney cortex by a cycloheximidesensitive process. J Clin Invest 65:1523–1526Google Scholar
  9. 9.
    Gilman AG (1970) A protein binding assay for adenosine 3′,5′-cyclic monophosphate. Proc. Natl Acad Sci USA 67:305–313Google Scholar
  10. 10.
    Lowry OH, Roseborough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  11. 11.
    Popovtzer MM, Robinette JB, DeLuca HF, Holick MF (1974) The acute effect of 25-hydroxycholecalciferol on renal handling of phosphorus. Evidence for a parathyroid hormone-dependent mechanism. J Clin Invest 53:913–921Google Scholar
  12. 12.
    Popovtzer MM, Robinette JB (1975) Effect of 25(OH)vitamin D3 on urinary excretion of cyclic adenosine monophosphate. Am J Physiol 229:907–910Google Scholar
  13. 13.
    Popovtzer MM, Blum MS, Flis RS (1977) Evidence for the interference of 25(OH)vitamin D3 with phosphaturic action of calcitonin. Am J Physiol 232:E515-E521Google Scholar
  14. 14.
    Popovtzer MM, Mehandru S, Saghafi D, Blum MS (1978) Interactions between PTH, vitamin D metabolites and other factors in tubular reabsorption of phosphate. Adv Expt Med Biol 103:11–19Google Scholar
  15. 15.
    Popovtzer MM, Wald H (1981) Evidence for interference of 25(OH)vitamin D3 with phosphaturic action of glucagon. Am J Physiol 240:F269-F275Google Scholar
  16. 16.
    Puschett JB, Kuhrman MS (1978) Renal tubular effects of 1,25-dihydroxy vitamin D3: interactions with vasopressin and parathyroid hormone. J Lab Clin Med 92:895–903Google Scholar
  17. 17.
    Puschett JB, Szramowski J (1978) Importance of 25-hydroxylation to the renal tubular actions of vitamin of metabolites. Adv Exp Biol Med 103:105–109Google Scholar
  18. 18.
    Singh RP, Bronner F (1980) Vitamin D acts posttranscriptionally—in vitro studies with the vitamin D-dependent calcium-binding protein of rat duodenum. In: Siegel FL, Carafoli E, Kreutsinger RH, MacLennan DH, Wasserman RH (eds) Calcium-binding proteins: structure and function. North-Holland, New York, pp 379–383Google Scholar
  19. 19.
    Tsai HC, Midgett RJ, Norman AW (1973) Studies on claciferol metabolism. VII. The effects of actinomycin D and cycloheximide on the metabolism, tissue and subcellular localization and action of vitamin D3. Arch Bioch Biophys 157:339–347Google Scholar
  20. 20.
    Wald H, Popovtzer MM (1980) Antagonistic effects of 25(OH)vitamin D3 and peptide hormones on the activation of adenylate cyclase/cyclic AMP system in renal tissue in vitro. Adv Exp Med Biol 128:625–633Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Meir Brezis
    • 1
  • Hanna Wald
    • 1
  • Ruth Shilo
    • 1
  • Mordecai M. Popovtzer
    • 1
  1. 1.Nephrology ServicesHadassah-Hebrew University School of MedicineJerusalemIsrael

Personalised recommendations