Calcium Signaling of Calcium-Binding Proteins and Drug Actions

  • Toshio Tanaka
  • Hiroyoshi Hidaka
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 255)


Intracellular calcium ion plays a critical role in cell activation in response to various agonists and calmodulin is a major intracellular receptor for calcium ion. At first, there is the formation of a calcium-calmodulin complex. Subsequently, the calcium-calmodulin complex interact with target proteins. Then, the target protein becomes active and transfer calcium signal to the next molecule. Recently, we have found many calmodulin antagonists with various chemical structures (Figure 1). These compounds selectively inhibit the process of interaction of the calcium-calmodulin complex with target proteins.


Mast Cell Myosin Light Chain Calcium Binding Protein Myosin Light Chain Kinase Calcium Entry Blocker 
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  1. 1.
    T. Godfraind, R. Miller, and M. Wibo, Calcium antagonism and calcium entry blockade., Pharmacological Reviews, 38(4):321 (1986).PubMedGoogle Scholar
  2. 2.
    H. Hidaka, T. Yamaki, M. Naka, T. Tanaka, H. Haigawara, and R. Kobayashi, Calcium-regulated modulator protein interacting agents inhibit muscle calcium-stimulated protein kinase and ATPase., Mol. Pharmacol., 17:66 (1980).PubMedGoogle Scholar
  3. 3.
    H. Itoh, T. Tanaka, Y. Mitani, and H. Hidaka, The binding of the calcium channel blocker, bepridil, to calmodulin., Biochem. Pharmacol., 35(2): 217 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    H. Umekawa, K. Yamakawa, K. Nunoki, N. Taira, T. Tanaka, and H. Hidaka, Inhibition of calmodulin function by CV-159, a novel dihydropyridine compound., Biochem. Pharmacol., 37(18):3377 (1988).PubMedCrossRefGoogle Scholar
  5. 5.
    J. C. Foreman, M. B. Hallett, and J. L. Mongar, Site of action of the antiallergic drugs cromoglycate and doxantrazole., Br. J. Pharmacol., 59:473 (1977).Google Scholar
  6. 6.
    T. C. Theoharides, W. Sieghart, P. Greengard, and T. C. Douglas, Antiallergic drug cromolyn may inhibit histamine secretion by regulating phosphorylation of a mast cell protein., Science, 207:80 (1980).PubMedCrossRefGoogle Scholar
  7. 7.
    A. F. Welton, and G. Wiggan, Antiallergic drugs do not act through antagonism of calmodulin., Fedn Proc. Fedn Am. Socs exp. Biol., 42:569 (1983).Google Scholar
  8. 8.
    T. Tanaka, M. Saitoh, M. Ito, T. Shin, M. Naka, K. Endo, and H. Hidaka, Inhibition of human platelet secretion and of Ca2+, calmodulin-dependent protein phosphorylation by the antiallergic agent, GMCHA., Biochem. Pharmacol., 37(13) 2537 (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Nishikawa, T. Tanaka, and H. Hidaka, Ca2+-calmodulin dependent phosphorylation and platelet secretion., Nature, 287:863 (1980).PubMedCrossRefGoogle Scholar
  10. 10.
    T. Tanaka, H. Umekawa, M. Saitoh, T. Ishikawa, T. Shin, M. Ito, H. Itoh, Y. Kawamotsu, H. Sugihara, and H. Hidaka, Modulation of calmodulin function and of Ca-induced smooth muscle contraction by the calmodulin antagonist, HT-74., Mol. Pharmacol., 29:264 (1986).PubMedGoogle Scholar
  11. 11.
    T. Tanaka, and H. Hidaka, Hydrophobic regions function in calmodulin-enzymes interactions., J. Biol. Chem., 255(23): 11078 (1980).PubMedGoogle Scholar
  12. 12.
    T. Janaka, T. Ohmura, and H. Hidaka, Hydrophobic interaction of the Ca2+-calmodulin complex with calmodulin antagonists: naphthalenesulfonamide derivatives., Mol. Pharmacol., 22:403 (1982).Google Scholar
  13. 13.
    T. Tanaka, and H. Hidaka, Hydrophobic regions of calcium-binding proteins exposed by calcium., Biochem. Int., 2:71 (1981).Google Scholar
  14. 14.
    T. Tanaka, H. Umekawa, T. Ohmura, and H. Hidaka, Calcium-dependent hydrophobic chromatography of calmodulin, S-100 protein and troponin-C., Biochim. Biophys. Acta., 787:158 (1984).PubMedCrossRefGoogle Scholar
  15. 15.
    J. M. Marcum, J. R. Dedman, B. R. Brinkley, and A. R. Means, Control of microtubule assembly-disassembly by calcium-dependent regulator protein., Proc. Natl. Acad. Sci. USA., 75:3771 (1978).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Toshio Tanaka
    • 1
    • 2
  • Hiroyoshi Hidaka
    • 1
    • 2
  1. 1.Department of Molecular and Cellular PharmacologyMie University School of MedicineEdobashi, Tsu 514Japan
  2. 2.Department of PharmacologyNagoya University School of MedicineShowa-ku, Nagoya 466Japan

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