Skip to main content
Log in

The interaction of aluminum and other metal ions with calcium-calmodulin-dependent phosphodiesterase

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

In the search for the mode of action of aluminum ions in dialysis encephalopathy, their interaction with calmodulin has been assessed, and compared with those of Ca2+, Pb2+, Mn2+, Hg2+ and Cd2+. The basal and calmodulin-dependent activity of phosphodiesterase was measured in the presence of the ions, and their binding to calmodulin was assessed by competition with 45Ca2+ in flow dialysis. Al3+, Mn2+, Hg2+, and Cd2+ cannot be regarded as exclusive calmodulin antagonists or agonists, but rather interact with the phosphodiesterase itself. Pb2+ however, mimicks Ca2+ in every system tested, and is active in the same concentration range as Ca2+. Our results indicate that the assumed role of Al3+ ions in dialysis encephalopathy or other neurological disturbances is not linked with calmodulin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

EGTA:

Ethyleneglycol-bis-(β-aminoethyl ether)

N,N,N′,N′:

tetraacetic acid

References

  • Alfrey AC (1984) Aluminium intoxication. N Engl J Med 310: 1113–1114

    Google Scholar 

  • Alfrey AC, LeGendre GR, Kaehny WD (1976) The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med 294: 184–188

    Google Scholar 

  • Andreoli SP, Bergstein JM, Sherrard DJ (1984) Aluminum intoxication from aluminum-containing phosphate binders in children with azotemia not undergoing dialysis. N Engl J Med 310: 1079–1084

    Google Scholar 

  • Butcher RW, Sutherland EW (1962) Adenosine 3′,5′-phosphate in biological material. I. Purification and properties of cyclic 3′,5′-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3′5′-phosphate in human urine. J Biol Chem 237: 1244–1250

    Google Scholar 

  • Chao SH, Suzuki Y, Zysk JR, Cheung WY (1984) Activation of calmodulin by various metal cations as a function of ionic radius. Mol Pharmacol 26: 75–82

    Google Scholar 

  • Chen PS, Toribara TY, Warner H (1956) Microdetermination of phosphorus. Anal Chem 28: 1750–1758

    Google Scholar 

  • Cheung WY (1969) Cyclic 3′5′-nucleotide phosphodiesterase: Preparation of a partially inactive enzyme and its subsequent stimulation by snake venom. Biochim Biophys Acta 191: 303–315

    Google Scholar 

  • Colowick SP, Womack FC (1969) Binding of diffusible molecules by macromolecules: rapid measurement by rate of dialysis. J Biol Chem 244: 774–777

    Google Scholar 

  • Feldmann K (1978) New devices for flow dialysis and ultrafiltration for the study of protein-ligand interactions. Anal Biochem 88: 225–235

    Google Scholar 

  • Fiske CH, SubbaRow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66: 375–400

    Google Scholar 

  • Goldstein GW, Ar D (1983) Lead activates calmodulin sensitive processes. Life Sci 33: 1001–1006

    Google Scholar 

  • Habermann E, Crowell K, Janicki P (1983) Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol 54: 61–70

    Google Scholar 

  • Howard JMH (1984) Clinical importance of small increases in serum aluminum. Clin Chem 30: 1722–1723

    Google Scholar 

  • Klee CB, Krinks MH (1978) Purification of cyclic 3′,5′-nucleotide phosphodiesterase inhibitory protein by affinity chromatography on activator protein coupled to sepharose. Biochemistry 126: 203–207

    Google Scholar 

  • Klee CB, Vanaman TC (1982) Calmodulin. Adv Protein Chem 35: 213–321

    Google Scholar 

  • Lin YM, Liu YP, Cheung WY (1974) Cyclic 3′∶5′-nucleotide phosphodiesterase. J Biol Chem 249: 4943–4954

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RF (1951) Protein measurement with the folin-phenol-reagent. J Biol Chem 193: 265–275

    Google Scholar 

  • Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83: 346–356

    Google Scholar 

  • Siegel N, Haug A (1983) Aluminum interaction with calmodulin. Evidence for altered structure and function from optical and enzymatic studies. Biochim Biophys Acta 744: 36–45

    Google Scholar 

  • Suhayda CG, Haug A (1984) Organic acids prevent aluminum-induced conformational changes in calmodulin. Biochem Biophys Res Commun 119: 376–381

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by a DFG fellowship

Part of the thesis of G. Federolf (FB 23, University of Giessen, FRG)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Richardt, G., Federolf, G. & Habermann, E. The interaction of aluminum and other metal ions with calcium-calmodulin-dependent phosphodiesterase. Arch Toxicol 57, 257–259 (1985). https://doi.org/10.1007/BF00324788

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00324788

Key words

Navigation