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Inhibition of renal adenylate cyclase by plasma from uremic patients

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Abstract

The native plasma of patients suffering from renal insufficiency inhibited the parathyroid hormone (PTH), the vasopressin (VP) and the NaF-activated adenylate cyclase (AC) in bovine renal plasma membranes. A crude immunoglobulin fraction, prepared by (NH4)2SO4precipitation, decreased only the hormone, but not the NaF activated AC. Chromatography of the native plasma on a AcA 34 column revealed two peaks inhibiting the PTH and to a lesser extent the VP dependent AC. Only the second peak reduced the NaF stimulated cAMP production. None of the column samples inhibited the isoproterenol stimulated adenylate cyclase in turkey red blood cells. Further purification of the first peak on a Sepharose 6B column confirmed previous results that immunoglobulins may block the PTH receptor in the kidney. Repurification of the second peak of inhibition on a Bio-Gel P10 column suggested that small peptides crossreacting in the radioimmunoassay for PTH may desensitize the hormonal receptor.

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References

  1. Arieff A.I., Massry S.G. Calcium metabolism of brain in acute renal failure. J. Clin. Invest. 53: 387, 1974.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Avram M.M., Jancu M., Morrow P., Feinfeld D., Huatuco A. Uremic syndrome in man: new evidence for parathor mone as a multisystem neurotoxin. 11: 59, 1979.

  3. Massry S.G., Popovtzer M.M., Coburn J.W., Maxwell M.H., Makoff D.L., Kleeman C.R. Intractable pruritus as a manifestation of secondary hyperparathyroidism in uremia. N. Engl.J. Med. 279: 697, 1968.

    Article  PubMed  CAS  Google Scholar 

  4. Massry S.G., Goldstein D.A. The search for uremic toxin(s) “X” “X” = PTH. Clin. Nephrol. 11: 181, 1979.

    PubMed  CAS  Google Scholar 

  5. Avram M.M., Alexis H., Rahman N., Son B., Jancu M. Decreased transfusional requirement following parathy roidectomy in long term hemodialysis. Proc. Am. Soc. Nephrol. 5: 5, 1971.

    Google Scholar 

  6. Bailey G.L., Griffith H.J.L., Merrill J.P. A vascular necrosis of the femoral head in patients on chronic hemodialysis. 18: 401, 1972.

  7. Cantin M. Kidney, parathyroid and lipemia. Lab. Invest. 14: 1691, 1965.

    PubMed  CAS  Google Scholar 

  8. Bogin E., Massay S.G., Harary J. Effect of parathyroid hormone on rat heart cells. J. Clin. Invest. 67: 1215, 1981.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Remuzzi G., Benigin A., Dodesini P., Schieppati A., Livio M., Poletti E., Mecca G., De-Gaetano G. Parathyroid hormone inhibits human platelet function. Lancet 1: 1321, 1981.

    Article  Google Scholar 

  10. Scribener B.H., Babb A.L. Evidence for toxins of “middle” molecular weight. Kidney Int. 7: 349, 1975.

    Google Scholar 

  11. Juppner H., Bialasiewcz A.A., Hesch R.D. Autoantibodies to parathyroid hormone receptor. Lancet 2: 1222, 1978.

    Article  PubMed  CAS  Google Scholar 

  12. Smith B.R., Hall R. Thyroid-stimulating immunoglobulins in Graves’ disease. Lancet 2: 427, 1974.

    Article  PubMed  CAS  Google Scholar 

  13. Kahn C.R., Flier J.S., Bar R.S., Archer J.A., Gordon P., Martin M.M., Roth J. The syndromes of insulin resistance and acanthosis nigricans. N. Engl.J. Med. 294: 739, 1976.

    Article  PubMed  CAS  Google Scholar 

  14. Patrick J., Lindström J.M. Autoimmune response to acetylcholine receptor. Science 180: 871, 1973.

    Article  PubMed  CAS  Google Scholar 

  15. Bronlik P.D., Ston J., Pacowsky V. Effect of chronical renal failure on inactivation of parathormone by rat kidney tissue slices. Physiol. Bohemoslov. 21: 239, 1972.

    Google Scholar 

  16. Fitzpatrick D.F., Davenport G.R., Forte L., Landon E.J. Characterization of plasma membrane proteins in mallian kidney.I. Preparation of a membrane fraction and separation of the protein, J. Biol. Chem. 244: 3561, 1969.

    PubMed  CAS  Google Scholar 

  17. Jüppner H., Mohr H., Hesch R.D. Adsorption of parathyrin: Pitfall for solid phase assays using radiolabeled antibodies? J. Clin. Chem. Clin. Biochem. 18: 585, 1980.

    PubMed  Google Scholar 

  18. Albano J.D.M., Maudsley D.V., Brown B.L., Barnes G.D. A simplified procedure for the determination of adenyl ate cyclase activity. Biochem. Soc. Trans. 1: 411, 1973.

    Google Scholar 

  19. Hunter W.M., Greenwood F.C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 194: 495, 1962.

    Article  PubMed  CAS  Google Scholar 

  20. Gardner J.D., Klaeveman H.L., Bilezikian J.P., Aurbach G.D. Effect of β-adrenergic catecholamines on sodium transport in turkey erythrocytes. J. Biol. Chem. 248: 5590, 1973.

    PubMed  CAS  Google Scholar 

  21. Hehrmann R., Wilke R., Nordmeyer J.P., Hesch R.D. Hochsensitiver, C-terminal-spezifischer Radioimmuno assay für menschliches Parathormon als Routineme thode. Dtsch. Med. Wochenschr. 101: 1726, 1976.

    PubMed  CAS  Google Scholar 

  22. Dom-Quint G., Montz R., Dietel M., Mohr H. PTH content and biological activity of P2-Hamburg. Acta Endocrinol. (Kbh.) (suppl.) 234: 120, 1980.

    Google Scholar 

  23. Hehrmann R., Normeyer J.P., Mohr H., Hesch R.D. Human parathyroid hormone: antibody characterization. J. Immunoassay 2: 151, 1980.

    Article  Google Scholar 

  24. Nolte H., Mühlen A.V.Z., Hesch R.D. unter Mitarbeit von I. Pape, Warnecke U., Jüppner H. Auswertung radioimmunologischer Bestimmungsmethoden durch “Spline Approximation”. J. Clin. Chem. Clin. Biochem. 14: 253, 1976.

    PubMed  CAS  Google Scholar 

  25. Yamada K., Saito Y., Tamura Y., Yamamoto M., Kumagai A. Effects of antibody to renal plasma membranes on urinary excretion of adenosin 3′, 5′-monophosphate and phosphate induced by parathyroid hormone infusion in rats. Endocrinology 106: 973, 1980.

    Article  PubMed  CAS  Google Scholar 

  26. Beck N., Singh H., Reed J.W., Davis B.H. Direct inhibitory effect of hypercalcemia on renal actions of parathyroid hormone. J. Clin. Invest. 53: 717, 1974.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Nielsen S.T., Neumann W.F. Effects of PTH and Ca2+ on renal adenyl cyclase. J. Supramol. Struct. 9: 391, 1978.

    Article  PubMed  CAS  Google Scholar 

  28. Rosenblatt M., Segre G.V., Potts J.T. Synthesis of a fragment of parathyroid hormone, bPTH-(28-48): An inhibitor of hormone cleavage in vivo. Biochemistry 16: 2811, 1977.

    Article  PubMed  CAS  Google Scholar 

  29. Waters M.J.W., Friesen H.G. Studies with anti-growth hormone receptor antibodies. J. Biol. Chem. 254, 6826, 1979.

    PubMed  CAS  Google Scholar 

  30. Wasner H. Cyclo AMP Antagonist, ein neuer Hormonbote. In: Rensing L., Roth G. (Eds.), Zelluläre Kommunikationsund Kontrollmechanismen, ed. 2. Frühjahrskolloquium der Universität Bremen, 1978, P. 207.

    Google Scholar 

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Authors and Affiliations

  1. Abteilung für Klinische Endokrinologie, Zentrum Innere Medizin, Karl-Wiechert-Allee 9, 3000, Hannover 61, Germany

    H. Jüppner & R. D. Hesch

Authors
  1. H. Jüppner
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  2. R. D. Hesch
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Additional information

This work was presented in part at the VI International Congress of Endocrinology, Melbourne, Australia, 1980.

Supported by the Deutsche Forschungsgemeinschaft (DFG) HE 593/12.

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Jüppner, H., Hesch, R.D. Inhibition of renal adenylate cyclase by plasma from uremic patients. J Endocrinol Invest 5, 303–309 (1982). https://doi.org/10.1007/BF03350518

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  • DOI: https://doi.org/10.1007/BF03350518

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