Mechanisms of NAD Action in Regulation of Renal Brush Border Membrane Transport of Phosphate

  • Stephen A. Kempson
  • Thomas P. Dousa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 208)


Many different hormonal and non-hormonal stimuli change the rate of phosphate (Pi) transport across the renal brush border membrane (BBM) (1,2, 3) which probably reflects the central role of proximal tubular reabsorption in renal handling of Pi. Based on considerations of (a) the time required for the effects of these stimuli to induce a response, and (b) whether the response is dependent upon intact de novo protein synthesis, it appears that the various stimuli may act intracellularly through at least two general mechanisms (2).


Brush Border Membrane Phosphate Transport Renal Brush Border Membrane Renal Brush Border Membrane Vesicle Brush Border Vesicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J.-P. Bonjour and J. Caverzasio, Phosphate transport in the kidney, Rev. Physiol. Biochem. Pharmacol. 100: 161 (1984).Google Scholar
  2. 2.
    S. A. Kempson and T. P. Dousa, Current concepts of regulation of phosphate transport in renal proximal tubules, Biochem. Pharmacol. in press.Google Scholar
  3. 3.
    T. P. Dousa and S. A. Kempson, Regulation of renal brush border membrane transport of phosphate, Min. Electrolyte Metab. 7: 113 (1982).Google Scholar
  4. 4.
    A. N. K. Yusufi, N. Murayama, M. J. Keller, and T. P. Dousa, Modulatory effect of thyroid hormones on uptake of phosphate and other solutes across luminal brush border membrane of kidney cortex. Endocrinology 116: 2438 (1985).CrossRefGoogle Scholar
  5. 5.
    S. T. Turner, G. M. Kiebzak, and T. P. Dousa, Mechanism of glucocorticoid effect on renal transport of Pi, Am. J. Physiol. 243: C227 (1982).Google Scholar
  6. 6.
    S. V. Shah, S. A. Kempson, T. E. Northrup, and T. P. Dousa, Renal adaptation to the low phosphate diet in rats; blockade by actinomycin D, J. Clin. Invest. 64: 955 (1979).CrossRefGoogle Scholar
  7. 7.
    A. N. K. Yusuf i, R. Holets, and T. P. Dousa, Mechanism by which T3 stimulates brush border membrane transport of phosphate, Abstracts 9th Int. Congress Nephrol. (Los Angeles, California) 378A (1984).Google Scholar
  8. 8.
    B. Sacktor and L. Noronha-Blob, Glucocorticoids act directly on renal cells to inhibit phosphate transport, Fed. Proc. 43: 632 (1984).Google Scholar
  9. 9.
    H. Evers, H. Murer, and R. Kinne, Effect of parathyrin on the transport properties of isolated renal brush border vesicles, Biochem. J. 172: 49 (1978).Google Scholar
  10. 10.
    M. R. Hammerman, I. E. Karl, and K. A. Hruska, Regulation of canine renal vesicle Pi transport by growth hormone and parathyroid hormone, Biochim. Biophys. Acta 603: 322 (1980).CrossRefGoogle Scholar
  11. 11.
    A. Yusuf i, T. Berndt, N. Murayama, F. Knox, and T. Dousa, The response of superficial and deep cortex to phosphaturic hormones in rats fed normal or low phosphate diets, Clin. Res. 32: 461A (1984).Google Scholar
  12. 12.
    M. R. Hammerman, S. Rogers, V. A. Hansen, and J. R. Gavin, Insulin stimulates Pi transport in brush border vesicles from proximal tubular segments, Am. J. Physiol. 247: E616 (1984).Google Scholar
  13. 13.
    B. S. Levine, K. Ho, A. Hodsman, K. Kurokawa, and J. W. Coburn, Early renal brush border membrane adaptation to dietary phosphorus, Min. Electrolyte Metab. 10: 222 (1984).Google Scholar
  14. 14.
    J. Caverzasio, C. D. A. Brown, J. Biber, J.-P. Bonjour, and H. Murer, Adaptation of phosphate transport in phosphate-deprived LLC-PK1 cells, Am. J. Physiol. 248: F122 (1985).Google Scholar
  15. 15.
    H. C. Rasmussen, C. Arnaud, and C. Hawker, Actinomycin D and the response to parathyroid hormone, Science 144: 1019 (1964).CrossRefGoogle Scholar
  16. 16.
    B. S. Levine, K. Kurokawa, and J. W. Coburn, Renal adaptation to diet phosphorus; early events, Abstracts 9th Int. Congress Nephrol. (Los Angeles, California) 55A (1984).Google Scholar
  17. 17.
    S. A. Kempson, G. Colon-Otero, S.-Y. L. Ou, S. T. Turner, and T. P. Dousa, Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat, J. Clin. Invest. 67: 1347 (1981).CrossRefGoogle Scholar
  18. 18.
    R. J. Lefkowitz and M. G. Caron, Adrenergic receptors; molecular mechanisms of clinically relevant regulation, Clin. Res. 33: 395 (1985).Google Scholar
  19. 19.
    T. P. Dousa, A. N. K. Yusuf i, E. Kusano, and J. L. Braun-Werness, Effect of nicotinamide administration on NAD content in proximal tubules, Kidney Int. 23: 222 (1983).Google Scholar
  20. 20.
    S. A. Kempson, S. T. Turner, A. N. K. Yusuf i, and T. P. Dousa, Actions of NAD on renal brush border transport of phosphate in vivo and in vivo, Am. J. Physiol. 249:in press (1985).Google Scholar
  21. 21.
    D. H. Williamson and J. T. Brosnan, Concentrations of metabolites in animal tissues, in: Methods of Enzymatic Analysis, H. U. Bergmeyer, ed., Academic Press, New York, vol. 4:2266 (1974).Google Scholar
  22. 22.
    J. L. Braun-Werness, B. A. Jackson, P. G. Werness, and T. P. Dousa, Binding of nicotinamide adenine dinucleotide by the renal brush border membrane from rat kidney cortex, Biochim. Biophys. Acta 732: 553 (1983).CrossRefGoogle Scholar
  23. 23.
    K. Ueda and O. Hayaishi, ADP-Ribosylation, Ann. Rev. Biochem. 54: 73 (1985).CrossRefGoogle Scholar
  24. 24.
    D. A. Yost and J. Moss, Amino acid-specific ADP-ribosylation, J. Biol. Chem. 258: 4926 (1983).Google Scholar
  25. 25.
    S. A. Kempson and N. P. Curthoys, NAD-dependent ADP-ribosyltransferase in renal brush border membranes, Am. J. Physiol. 245: C449 (1983).Google Scholar
  26. 26.
    S. Filetti and B. Rapoport, Hormonal stimulation of eucaryotic cell ADPribosylation. Effect of thyrotropin on thyroid cells, J. Clin. Invest. 68: 461 (1981).CrossRefGoogle Scholar
  27. 27.
    M. J. S. DeWolf, P. Vitti, F. S. Ambesi-Impiombato, and L. D. Kohn, Thyroid membrane ADP ribosyltransferase activity, J. Biol. Chem. 256: 12287 (1981).Google Scholar
  28. 28.
    D. M. Gill and R. Meren, ADP-ribosylation of membrane proteins catalysed by cholera toxin; basis of the activation of adenylate cyclase, Proc. Nat. Acad. Sci. USA 75: 3050 (1978).CrossRefGoogle Scholar
  29. 29.
    H. R. Kaslow, V. E. Groppi, M. E. Abood, and H. E. Bourne, Cholera toxin can catalyze ADP-ribosylation of cytoskeletal proteins, J. Cell Biol. 91: 410 (1981).CrossRefGoogle Scholar
  30. 30.
    D. J. Hawkins and E.T. Browning, Tubulin adenosine diphosphate ribosylation is catalysed by cholera toxin, Biochemistry 21: 4474 (1982).CrossRefGoogle Scholar
  31. 31.
    M. R. Hammerman, D. E. Cohn, J. Tamayo, and K. J. Martin, PTH increases ADP-ribosylation of canine renal brush border membrane proteins, Kidney Int. 23: 100 (1983).Google Scholar
  32. 32.
    S. A. Kempson, NAD-Glycohydrolase in renal brush border membranes, Am. J. Physiol. 249: F366 (1985).Google Scholar
  33. 33.
    H. F. Bunn, R. Shapiro, M. McManus, L. Garrick, M. J. McDonald, P. M. Gallop, and K. H. Gabbay, Structural heterogeneity of human hemoglobin A due to non-enzymatic glycosylation, J. Biol. Chem. 254: 3892 (1979).Google Scholar
  34. 34.
    O. H. Wieland, Protein modification by non-enzymatic glucosylation; possible role in the development of diabetic complications, Mol. Cell. Endocrinol. 29: 125 (1983).CrossRefGoogle Scholar
  35. 35.
    E. Kun, A. C. Y. Chang, M. L. Sharma, A. M. Ferro, and D. Nitecki, Covalent modification of proteins by metabolites of NAD+, Proc. Nat. Acad. Sci. USA 73: 3131 (1976).CrossRefGoogle Scholar
  36. 36.
    H. Hilz, R. Koch, W. Fanick, K. Klapproth, and P. Adamietz, Nonenzymic ADP-ribosylation of specific mitochondrial polypeptides, Proc. Nat. Acad. Sci. USA 81: 3929 (1984).CrossRefGoogle Scholar
  37. 37.
    B. M. Olivera, Z. W. Hall, Y. Anraku, J. R. Chien, and I. R. Lehman, On the mechanism of the polynucleotide joining reaction, Cold Spring Harbor Symp. Quant. Biol. 33: 27 (1968).CrossRefGoogle Scholar
  38. 38.
    R. I. Gumport and I. R. Lehman, Structure of the DNA ligase-adenylate intermediate; lysine (E-amino)-linked adenosine monophosphoramidate, Proc. Nat. Acad. Sci. USA 68: 2559 (1971).CrossRefGoogle Scholar
  39. 39.
    S. C. B. Yan, An unexpected twist in the reversal of ADP-ribosylation, Trends Biochem. Sci. 9: 331, (1984).CrossRefGoogle Scholar
  40. 40.
    H. Okayama, M. Honda, and O. Hayaishi, Novel enzyme from rat liver that cleaves an ADP-ribosyl histone linkage, Proc. Nat. Acad. Sci. USA 75: 2254 (1978).CrossRefGoogle Scholar
  41. 41.
    J. Oka, K. Ueda, O. Hayaishi, H. Komura, and K. Nakanishi, ADP-ribosyl protein lyase. Purification, properties and identification of the product, J. Biol. Chem. 259: 986 (1984).Google Scholar
  42. 42.
    K. P. Smith, R. C. Benjamin, J. Moss, and M. K. Jacobson, Identification of enzymatic activities which process protein bound mono(ADP-ribose), Biochem. Biophys. Res. Commun. 126: 136 (1985).CrossRefGoogle Scholar
  43. 43.
    M. R. Hammerman, V. A. Hansen, and J. J. Morrissey, ADP-ribosylation of canine renal brush border membrane vesicle proteins is associated with decreased phosphate transport, J. Biol. Chem. 257: 12380 (1982).Google Scholar
  44. 44.
    R. P. Lang, N. Yanagawa, E. P. Nord, L. Sakhrani, S. H. Lee, and L. G. Fine, Nucleotide inhibition of phosphate transport in the renal proximal tubule, Am. J. Physiol. 245: F263 (1983).Google Scholar
  45. 45.
    H. S. Tenenhouse and Y. L. Chu, Hydrolysis of nicotinamide-adenine dinucleotide by purified renal brush border membranes, Biochem. J. 204: 635 (1982).Google Scholar
  46. 46.
    M. R. Hammerman, V. M. Corpus, and J. J. Morrissey, NAD+-induced inhibition of phosphate transport in canine renal brush border membranes. Mediation through a process other than or in addition to NAD+ hydrolysis, Biochim. Biophys. Acta 732: 110 (1983).CrossRefGoogle Scholar
  47. 47.
    P. Gmaj, J. Biber, S. Angielski, G. Stange, and H. Murer, Intravesicular NAD has no effect on sodium-dependent phosphate transport in isolated renal brush border membrane vesicles, Pfluegers Arch. 400: 60 (1984).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Stephen A. Kempson
    • 1
    • 2
  • Thomas P. Dousa
    • 1
    • 2
  1. 1.Department of Physiology and BiophysicsIndiana University Medical SchoolIndianapolisUSA
  2. 2.Nephrology Research UnitMayo Clinic and Mayo Medical SchoolRochesterUSA

Personalised recommendations