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Mechanisms of Pharmacologically Altering Calmodulin Activity

  • Chapter
Calcium in Biological Systems

Abstract

Considerable evidence has now accumulated indicating that calmodulin is the principal mediator of the effects of Ca2+ in most eukaryotic cells [for reviews see 3,8,24,25]. Since calmodulin plays such a fundamental role in cell biology, agents that inhibit its activity should produce important pharmacological effects. An understanding of the mechanisms by which drugs alter calmodulin activity may suggest new approaches for modifying various physiological or pathological processes. Furthermore, the development of selective calmodulin antagonists may provide a useful means for further studying the biological roles of calmodulin.

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References

  1. Adunyah, E. S.; Niggli, V.; Carafoli, E. The anticalmodulin drugs trifluoperazine and R 24 571 remove the activation of the purified erythrocyte Ca2+ -ATPase by acidic phospholipids and by controlled proteolysisFEES Lett 143: 65–68, 1982.

    Article  CAS  Google Scholar 

  2. Blumenthal, D. K.; Stull, J. T. Activation of skeletal muscle myosin light chain kinase by calcium (2+) and calmodulinBiochemistry 19: 5608–5614, 1980.

    Article  PubMed  CAS  Google Scholar 

  3. Brostrom, C. O.; Wolff, D. J. Properties and functions of calmodulinBiochem. Pharmacol 30: 1395–1405, 1981.

    Article  PubMed  CAS  Google Scholar 

  4. Brostrom, S.-L.; Bengt, L.; Mardh, S.; Forsen, S.; Thulin, E. Interaction of the antihypertensive drug felodipine with calmodulinNature (London) 292: 777–778, 1981.

    Article  Google Scholar 

  5. Burgess, W. H. Characterization of calmodulin and calmodulin isotypes from sea urchin gametesJ. Biol. Chem 257: 1800–1804, 1982.

    PubMed  CAS  Google Scholar 

  6. Chafouleas, J. G.; Dedman, J. R.; Munjaal, R. P.; Means, A. R. Calmodulin: Development and application of a sensitive radioimmunoassayJ. Biol. Chem 254: 10262–10267, 1979.

    PubMed  CAS  Google Scholar 

  7. Chao, S. H.; Suzuki, Y.; Zysk, J. R.; Cheung, W. Y. Metal cation-induced activation of calmodulin is a function of ionic radiiFed. Proc 42: 1087, 1983.

    Google Scholar 

  8. Cheung, W. Y. Calmodulin plays a pivotal role in cellular regulationScience 207: 19–27, 1980.

    Article  PubMed  CAS  Google Scholar 

  9. Comte, M.; Maulet, Y.; Cox, J. A. Ca2+ -dependent high-affinity complex formation between calmodulin and melittinBiochem. J 209: 269–272, 1983.

    PubMed  CAS  Google Scholar 

  10. Cox, J. A.; Comte, M.; Stein, E. A. Activation of human erythrocyte Ca2+-dependent Mg2+-activated ATPase by calmodulin and calcium: Quantitative analysisProc. Natl. Acad. Sci. USA 79: 4265–4269, 1982.

    Article  PubMed  CAS  Google Scholar 

  11. Cox, J. L.; Harrison, S. D. Correlation of metal toxicity with in vitro calmodulin inhibitionBiochem. Biophys. Res. Commun 115: 106–111, 1983.

    Article  PubMed  CAS  Google Scholar 

  12. DeLorenzo, R. J.; Burdette, S.; Holderness, J. Benzodiazepine inhibition of the calcium-calmodulin protein kinase system in brain membraneScience 213: 546–549, 1981.

    Article  PubMed  CAS  Google Scholar 

  13. Earl, C. Q.; Prozialeck, W. C.; Weiss, B. Interaction of alpha adrenergic antagonists with calmodulinLife Sci 35: 525–534, 1984.

    Google Scholar 

  14. Epstein, P. M.; Fiss, K.; Hachisu, R.; Andrenyak, D. M. Interaction of calcium antagonists with cyclic AMP phosphodiesterases and calmodulinBiochem. Biophys. Res. Commun 105: 1142–1149, 1982.

    Article  PubMed  CAS  Google Scholar 

  15. Forsen, S.; Thulin, E.; Drakenberg, T.; Krebs, J.; Seamon, K. A 113Cd NMR study of calmodulin and its interaction with calcium, magnesium and trifluoperazineFEBS Lett 117: 189–194, 1980.

    Article  PubMed  CAS  Google Scholar 

  16. Gietzen, K.; Delgado, E. S.; Bader, H. Compound 48/80: A powerful and specific inhibition of calmodulin- dependent Ca2+-transport ATPaseIRCS Med. Sci. Biochem 11: 12–13, 1983.

    CAS  Google Scholar 

  17. Gietzen, K.; Sadorf, I.; Bader, H. A model for the regulation of the calmodulin-dependent enzymes erythrocyte Ca2+-transport ATPase and brain phosphodiesterase by activators and inhibitorsBiochem.J 207: 541–548, 1982.

    PubMed  CAS  Google Scholar 

  18. Hidaka, H.; Asano, M.; Tanaka, T. Activity-structure relationship of calmodulin antagonists: Naphthalenesulfonamide derivativesMol. Pharmacol 20: 571–578, 1981.

    PubMed  CAS  Google Scholar 

  19. Hidaka, H.; Yamaki, T.; Naka, M.; Tanaka, T.; Hayashi, H.; Kobayashi, R. Calcium-regulated modulator protein interacting agents inhibit smooth muscle calcium-stimulated protein kinase and ATPaseMol. Pharmacol 17: 66–72, 1980.

    PubMed  CAS  Google Scholar 

  20. Huang, C. Y.; Chau, V.; Chock, P. B.; Wang, J. H.; Sharma, R. K. Mechanism of activation of cyclic nucleotide phosphodiesterase: Requirement of the binding of four Ca2+ to calmodulin for activationProc. Natl. Acad. Sci. USA 78: 871–874, 1981.

    Article  PubMed  CAS  Google Scholar 

  21. Kakiuchi, S.; Yasuda, S.; Yamazaki, R.; Teshima, Y.; Kanda, K.; Kakiuchi, R.; Sobue, K. Quantitative determinations of calmodulin in the supernatant and particulate fractions of mammalian tissuesJ. Biochem. (Tokyo) 92: 1041–1048, 1982.

    CAS  Google Scholar 

  22. Katoh, N.; Wise, B. C.; Wrenn, R. W.; Kuo, J. F. Inhibition by adriamycin of calmodulin-sensitive and phospholipid-sensitive calcium-dependent phosphorylation of endogenous proteins from heartBiochem. J 198: 199–205, 1981.

    PubMed  CAS  Google Scholar 

  23. Kilimann, M.; Heilmeyer, L. M. G. The effect of Mg2 + on the Ca2 +-binding properties of non-activated phosphorylase kinaseEur. J. Biochem 73: 191–197, 1977.

    Article  PubMed  CAS  Google Scholar 

  24. Klee, C. B. Calmodulin: Structure-function relationships. In: Calcium and Cell Function, volume 1, W. Y. Cheung, ed., New York, Academic Press, 1980, pp. 59–77.

    Google Scholar 

  25. Klee, C. B.; Crouch, T. H.; Richman, P. G. CalmodulinAnnu. Rev. Biochem 49: 489–515, 1980.

    Article  PubMed  CAS  Google Scholar 

  26. Kurn, N. Inhibition of phosphate uptake by fluphenazine, a calmodulin inhibitor: Analysis of Volvox wild-type and fluphenazine resistant mutant strainsFEBS Lett 144: 68–72, 1982.

    Article  PubMed  CAS  Google Scholar 

  27. Kurn, N.; Sela, B.-A. Altered calmodulin activity in fluphenazine-resistant mutant strains: Pleiotropic effect on development and cellular organization in Volvox carteriEur. J. Biochem 121: 53–57, 1981.

    Article  PubMed  CAS  Google Scholar 

  28. Levin, R. M.; Weiss, B. Mechanism by which psychotropic drugs inhibit adenosine cyclic 3′, ′-monophosphate phosphodiesterase of brainMol. Pharmacol 12: 581–589, 1976.

    PubMed  CAS  Google Scholar 

  29. Levin, R. M.; Weiss, B. Binding of trifluoperazine to the calcium-dependent activator of cyclic nucleotide phosphodiesteraseMol. Pharmacol 13: 690–697, 1977.

    PubMed  CAS  Google Scholar 

  30. Levin, R. M.; Weiss, B. Specificity of the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase and to a series of other calcium-binding proteinsBiochim. Biophys. Acta 540: 197–204, 1978.

    PubMed  CAS  Google Scholar 

  31. Levin, R. M.; Weiss, B. Selective binding of antipsychotics and other psychoactive agents to the calcium- dependent activator of cyclic nucleotide-phosphodiesteraseJ. Pharmacol. Exp. Ther 208: 454–459, 1979.

    PubMed  CAS  Google Scholar 

  32. Lin, Y. M.; Liu, Y. P.; Cheung, W. Y. Cyclic 3′:5′-nucleotide phosphodiesterase: Purification, characterization and active form of the protein activator from bovine brainJ. Biol. Chem 249: 4943–4954, 1974.

    PubMed  CAS  Google Scholar 

  33. Luthra, M. G. Trifluoperazine inhibition of calmodulin-sensitive Ca2+-ATPase and calmodulin-insensitive (Na+ + K +)- and Mg2+-ATPase activities of human and rat red blood cellsBiochim. Biophys. Acta 692: 271–277, 1982.

    Article  PubMed  CAS  Google Scholar 

  34. Malencik, D. A.; Anderson, S. R. Binding of hormones and neuropeptides by calmodulinBiochemistry 22: 1995–2001, 1983.

    Article  PubMed  CAS  Google Scholar 

  35. Malnoe, A.; Cox, J. A.; Stein, E. A. Ca2+ -dependent regulation of calmodulin binding and adenylate cyclase activation in bovine cerebellar membranesBiochim. Biophys. Acta 714: 84–92, 1982.

    PubMed  CAS  Google Scholar 

  36. Prozialeck, W. C. Structure-activity relationships of calmodulin antagonistsAnnu. Rep. Med. Chem 18: 203–212, 1983.

    Article  CAS  Google Scholar 

  37. Prozialeck, W. C.; Cimino, M.; Weiss, B. Photoaffinity labeling of calmodulin by phenothiazine antipsychoticsMol. Pharmacol 19: 264–269, 1981.

    PubMed  CAS  Google Scholar 

  38. Prozialeck, W. C.; Wallace, T. L.; Weiss, B. Chlorpromazine-linked calmodulin: A novel calmodulin antagonistFed. Proc 42: 1087, 1983.

    Google Scholar 

  39. Prozialeck, W. C.; Weiss, B. Inhibition of calmodulin by phenothiazines and related drugs: Structure-activity relationshipsJ. Pharmacol. Exp. Ther 222: 509–516, 1982.

    PubMed  CAS  Google Scholar 

  40. Roufogalis, B. D. Phenothiazine antagonism of calmodulin: A structurally-nonspecific interactionBiochem. Biophys. Res. Commun 98: 607–613, 1981.

    Article  PubMed  CAS  Google Scholar 

  41. Seeman, P. Anti-schizophrenic drugs: Membrane receptor sites of actionBiochem. Pharmacol 26: 1741–1748, 1977.

    Article  PubMed  CAS  Google Scholar 

  42. Sellinger-Barnette, M.; Weiss, B. Interaction of ß-endorphin and other opioid peptides with calmodulinMol. Pharmacol 21: 86–91, 1982.

    PubMed  CAS  Google Scholar 

  43. Sellinger-Barnette, M.; Weiss, B. Interaction of various peptides with calmodulinAdv. Cyclic Nucleotide Protein Phosphorylation Res 16: 261–276, 1984.

    PubMed  CAS  Google Scholar 

  44. Sharma, R. K.; Wang, J. H. Inhibition of calmodulin-activated cyclic nucleotide phosphodiesterase by Triton X-100Biochem. Biophys. Res. Commun 100: 710–715, 1981.

    Article  PubMed  CAS  Google Scholar 

  45. Shimizu, T.; Hatano, M.; Nagao, S.; Nozawa, Y. 43Ca NMR studies of Ca2 + -Tetrahymena calmodulin complexesBiochem. Biophys. Res. Commun 106: 1112–1118, 1982.

    Article  PubMed  CAS  Google Scholar 

  46. Tanaka, T.; Hidaka, H. Interaction of local anesthetics with calmodulinBiochem. Biophys. Res. Commun 101: 447–453, 1981.

    Article  PubMed  CAS  Google Scholar 

  47. Teo, T. S.; Wang, J. H. Mechanism of activation of a cyclic adenosine 3′:5′ monophosphate phosphodiesterase from bovine heart by Ca2+ ionsJ. Biol. Chem 248: 5950–5955, 1973.

    PubMed  CAS  Google Scholar 

  48. Van Belle, H. R 24 571: A potent inhibitor of calmodulin-activated enzymesCell Calcium 2: 483–494, 1981.

    Article  Google Scholar 

  49. Volpi, M.; Sha’afi, R. I.; Epstein, P. M.; Andrenyak, D. M.; Feinstein, M. B. Local anesthetics, mepacrine and propranolol are antagonists of calmodulinProc. Natl. Acad. Sci. USA 78: 795–799, 1981.

    Article  PubMed  CAS  Google Scholar 

  50. Volpi, M.; Sha’afi, R. I.; Feinstein, M. B. Antagonism of calmodulin by local anesthetics: Inhibition of calmodulin-stimulated calcium transport of inside-out membrane vesiclesMol. Pharmacol 20: 363–370, 1981.

    PubMed  CAS  Google Scholar 

  51. Watanabe, K.; West, W. L. Calmodulin, activated cyclic nucleotide phosphodiesterase, microtubules, and vinca alkaloidsFed. Proc 41: 2292–2299, 1982.

    PubMed  CAS  Google Scholar 

  52. Watanabe, K.; Williams, E. F.; Law, J. S.; West, W. L. Effects of vinca alkaloids on calcium-calmodulin regulated cyclic adenosine 3′,5′-monophosphate phosphodiesterase activity from brainBiochem. Pharmacol 30: 335–340, 1981.

    Article  PubMed  CAS  Google Scholar 

  53. Weiss, B. Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesteraseAdv. Cyclic Nucleotide Res 5: 195–211, 1975.

    PubMed  CAS  Google Scholar 

  54. Weiss, B.; Fertel, R.; Figlin, R.; Uzunov, P. Selective alteration of the activity of the multiple forms of adenosine 3′,5′-monophosphate phosphodiesterase of rat cerebrumMol. Pharmacol 10: 615–625, 1974.

    CAS  Google Scholar 

  55. Weiss, B.; Hait, W. N. Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agentsAnnu. Rev. Pharmacol. Toxicol 17: 441–477, 1977.

    Article  PubMed  CAS  Google Scholar 

  56. Weiss, B.; Prozialeck, W. C.; Cimino, M.; Barnette, M. S.; Wallace, T. L. Pharmacological regulation of calmodulinAnn. N.Y. Acad. Sci 356: 319–345, 1980.

    Article  PubMed  CAS  Google Scholar 

  57. Weiss, B.; Prozialeck, W. C.; Wallace, T. L. Interaction of drugs with calmodulin: Biochemical, pharmacological and clinical implicationsBiochem. Pharmacol 31: 2217–2226, 1982.

    Article  PubMed  CAS  Google Scholar 

  58. Weiss, B.; Sellinger-Barnette, M. Effects of antipsychotic dopamine antagonists and polypeptide hormones on calmodulin. In: Apomorphine and Other Dopaminomimetics, Volume 1, G. L. Gessa and G. U. Corsini, eds., New York, Raven Press, 1981, pp. 179–192.

    Google Scholar 

  59. Weiss, B.; Wallace, T. L. Mechanisms and pharmacological implications of altering calmodulin activity. In: Calcium and Cell Function, Volume 1, W. Y. Cheung, ed., New York, Academic Press, 1980, pp. 329–379.

    Google Scholar 

  60. Zavecz, J. H.; Jackson, T. E.; Limp, G. L.; Yellin, T. O. Relationship between anti-diarrheal activity and binding to calmodulinEur. J. Pharmacol 78: 375–377, 1982.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, 19131, USA

    Walter C. Prozialeck

  2. Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, Pennsylvania, 19129, USA

    Benjamin Weiss

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  1. Walter C. Prozialeck
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  2. Benjamin Weiss
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Editors and Affiliations

  1. Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, USA

    Ronald P. Rubin  & James W. Putney Jr.  & 

  2. CIBA-GEIGY Corporation, Summit, New Jersey, USA

    George B. Weiss

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© 1985 Plenum Press, New York

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Prozialeck, W.C., Weiss, B. (1985). Mechanisms of Pharmacologically Altering Calmodulin Activity. In: Rubin, R.P., Weiss, G.B., Putney, J.W. (eds) Calcium in Biological Systems. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2377-8_30

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  • DOI: https://doi.org/10.1007/978-1-4613-2377-8_30

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