Interaction of Vitamin D-Metabolites with Adenylate Cyclase/Cyclic AMP System: A Biological Model of Controlled Regulation

  • Mordecai M. Popovtzer
  • Hanna Wald
  • Michael M. Friedlaender
  • Dvora Rubinger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 208)


Parathyroid hormone and other peptide hormones convey their biological messages by combining with membrane-bound receptors and activating them. The message is advanced then by catalitically generated cyclic AMP which carries the signal to the effector components of the cytosol, leading ultimately to the physiological response. The factors which control the operation of this system have not been delineated in detail yet. Such factors if present may exert their effect at any level of the activation cascade. For example inhibitors of phosphodiesterase may enhance the effect of adenylate cyclase agonists by blocking the degradation of cyclic AMP. In contrast, depletion of intracellular ATP which serves as a substrate for the generation of cyclic AMP may abolish the response to peptide hormones. We have recently demonstrated refractoriness of the kidney to parathyroid hormone in rats with maleate-induced Fanconi syndrome.1 In these animals the absence of phosphaturic response and the absence of augmented excretion of urinary cyclic AMP after the administration of parathyroid hormone was not due to altered function of the receptor complex but due to documented lack of ATP. Addition of ATP to the in vitro system restored to normal the response to parathyroid hormone as reflected by enhanced generation of cyclic AMP. The question which requires further investigations is whether variations in intracellular ATP may play a role in the physiological response to parathyroid hormone and other adenylate cyclase agonists.


Parathyroid Hormone Adenylate Cyclase Peptide Hormone Fanconi Syndrome Renal Handling 
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  1. 1.
    H. Wald, and M. M. Popovtzer, Renal refractoriness to parathyroid hormone in experimental Fanconi syndrome. Evidence for intact adenylate cyclase activation. Pfluegers Arch. 402: 116 (1984).CrossRefGoogle Scholar
  2. 2.
    M. M. Popovtzer, J. B. Robinette, K. M. McDonald, C. K. Kuruvila, The effect of hypercalcemia on renal handling of phosphorus. Evidence for two reabsorptive mechanisms. Amer. J. Physiol. 229: 901 (1975).Google Scholar
  3. 3.
    H. Wald, and M. M. Popovtzer, Effect of divalent ions on basal and hormone-activated renal adenylate cyclase/cyclic AMP system. Min. Electr. Metab. 10: 133 (1983).Google Scholar
  4. 4.
    M. M. Popovtzer, J. Robinette, H. DeLuca, and M. F. Holic, The acute effect of 25(OH) cholecalciferon on renal handling of phosphorus. Evidence for parathyroid hormone dependent mechanism. J. Clin. Invest. 53: 913 (1974).CrossRefGoogle Scholar
  5. 5.
    M. M. Popovtzer, and J. B. Robinette, The effect of 25-OH-vitamin D3 on renal handling of phosphorus. Evidence for inhibition of cyclic monophosphate formation. Amer. J. Physiol. 229: 907 (1975).Google Scholar
  6. 6.
    M. M. Popovtzer, R. S. Flis, and M. Blum, The effect of 25(OH)vit D3 on renal handling of phosphorus: Evidence for interference with the phosphaturic action of calcitonin. Amer. J. Physiol. 232: 515 (1977).Google Scholar
  7. 7.
    M. M. Popovtzer, and H. Wald, Evidence for interference of 25(OH)vitamin D3 with phosphaturic action of glucagon. Amer. J. Physiol. 240: F269 (1981).Google Scholar
  8. 8.
    M. M. Friedlaender, Z. Kornberg, H. Wald, and M. M. Popovtzer, Renal response to la(OH)vitamin D3 and 24,25(OH)2 vitamin D3: Evidence for the essential role of 25(OH) group. Amer. J. Physiol. 13: F674 (1983).Google Scholar
  9. 9.
    A. Edelman, M. Garabedian, I. Anagnostopoulos, and S. Balsan, Vitamin D and steroids. Rapid effect on membrane potential of hypertrophic chandrocytes and proximal tubular cells, in: “Vitamin D. A Chemical and Biochemical and Clinical Update,” W. de Gruyter & Co., Berlin & New York, p. 433 (1985).Google Scholar
  10. 10.
    G. S. Reddy, and J. D. Johnson, in: Proc. VIIth International Conference on Calcium Regulating Hormones. Abstract p. 4, Tokyo, Japan (1983).Google Scholar
  11. 11.
    M. M. Popovtzer, Interactions between PTH, vitamin D metabolites and other factors in tubular reabsorption of phosphate. Adv. Exp. Med. Biol. 103: 11 (1978).Google Scholar
  12. 12.
    D. Rubinger, and M. M. Popovtzer, Unpublished observations.Google Scholar
  13. 13.
    B. D. Catherwood, and J. E. Rubin, Interaction of 1,25(OH)2D with cAMP class of biological signals, in: “Vitamin D, A Chemical and Biochemical and Clinical Update,” W. de Gruyter & Co., Berlin & New York, p. 229 (1985).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Mordecai M. Popovtzer
    • 1
  • Hanna Wald
    • 1
  • Michael M. Friedlaender
    • 1
  • Dvora Rubinger
    • 1
  1. 1.Nephrology and Hypertension ServicesHadassah University HospitalJerusalemIsrael

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