Skip to main content
SpringerLink
Log in

Pyrazole Derivative Attenuates Store-Dependent Ca2+ Entry in Rat Peritoneal Macrophages

  • Published:
Cell and Tissue Biology Aims and scope Submit manuscript

Abstract—

Store-dependent Ca2+ entry is a ubiquitous mechanism of regulated Ca2+ entry into eukaryotic cells. It is activated upon depletion of intracellular Ca2+ stores and is involved in the regulation of a wide range of cellular processes. To elucidate the pharmacological characteristics of store-dependent Ca2+ entry into cells, we studied the effect of YM-58483, pyrazole derivative immunosuppressant, on the store-dependent Ca2+ entry in rat peritoneal macrophages induced by the endoplasmic Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid, as well as the disulfide-containing immunomodulators glutoxim and molixan. Using Fura-2AM, fluorescent calcium indicator, it has been shown for the first time that, in rat peritoneal macrophages, as well as in other cell types, pyrazole derivative YM-58483 effectively inhibits store-dependent Ca2+ entry and is a useful pharmacological tool to study the store-dependent Ca2+ entry in macrophages. The data obtained additionally confirm that Ca2+ entry induced by glutoxim or molixan is realized via the store-dependent mechanism.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

  1. Albarran, L., Lopez, J.J., Salido, G.M., and Rosado, J.A., Historical overview of store-operated Ca2+ entry, in Calcium Entry Pathways in Non-Excitable Cells, Wien: Springer-Verlag, 2016, p. 3.

    Google Scholar 

  2. Antushevich, A.A., Antonov, V.G., Grebenyuk, A.N., Antushevich, A.E., Ladanova, T.V., and Burova, E.B., Pathophysiological rationale of effectiveness of glutoxim suppor-tive therapy add-on to radiotherapy management of oropharyngeal cancer, Vestn. Ross. Voenno-Med. Akad., 2013, vol. 3, no. 43, p. 32.

    Google Scholar 

  3. Azimi, I., Flanagan, J.U., Stevenson, R.J., Inserra, M., Vetter, I., Monteith, G.R., and Denny, W.A., Evaluation of known and novel inhibitors of Orai1-mediated store-ope-rated Ca2+ entry in MDA-MB-231 breast cancer cells using a fluorescence imaging plate reader assay, Bioorg. Med. Chem., 2017, vol. 25, p. 440.

    Article  CAS  PubMed  Google Scholar 

  4. Berridge, M.J., Bootman, M.D., and Lipp, P., Calcium, a life and death signal, Nature, 1998, vol. 395, p. 645.

    Article  CAS  PubMed  Google Scholar 

  5. Berridge, M.J., Lipp, P., and Bootman, M.D., The versati-lity and universality of calcium signalling, Nat. Rev. Mol. Cell Biol., 2000, vol. 1, p. 11.

    Article  CAS  PubMed  Google Scholar 

  6. Berridge, M.J., Bootman, M.D., and Roderick, H.L., Calcium signalling: dynamics, homeostasis and remodeling, Nat. Rev. Mol. Cell Biol., 2003, vol. 4, p. 517.

    Article  CAS  PubMed  Google Scholar 

  7. Bird, G.S. and Putney, J.W., Pharmacology of store-ope-rated calcium entry channels, in Calcium Entry Channels in Non-Excitable Cells, CRC Press, 2018, p. 311.

    Google Scholar 

  8. Bogeski, I., Al-Ansary, D., Qu, B., Niemeyer, B.A., Hoth, M., and Peinelt, Ch., Pharmacology of ORAI channels as a tool to understand their physiological functions, Expert. Rev. Clin. Pharmacol., 2010, vol. 3, p. 291.

    Article  CAS  PubMed  Google Scholar 

  9. Borisov, A.E., Kozhemyakin, L.A., Antushevich, A.E., Ketliskaya, O.S., Kashchenko, V.A., Chepur, S.V., Katsa-lucha, V.V., Vasyukova, E.L., Novichenkov, A.O., and Motushchuk, I.E., Clinical and experimental grounds of the regional and systemic administration of the thiopoetin group medicines for cirrhosis of the liver. First communication, Vestn. Khirur. im. I.I. Grekova, 2001, vol. 4, no. 2, p. 32.

    Google Scholar 

  10. Bruce, J.I.E. and Elliott, A.C., Pharmacological evaluation of the role of cytochrome P450 in intracellular calcium signaling in rat pancreatic acinar cells, Brit. J. Physiol., 2000, vol. 131, p. 761.

    CAS  Google Scholar 

  11. Conrad, R.E., Induction and collection of peritoneal exudate macrophages, in Manual of Macrophages Methodology, New York: Marcell Dekker, 1981, p. 5.

    Google Scholar 

  12. Derler, I., Schindl, R., Fritsch, R., Heftberger, P., Riedl, M.Ch., Begg, M., House, D., and Romanin, Ch., The action of selective CRAC channel blockers is affected by the Orai pore geometry, Cell Calcium, 2013, vol. 53, p. 139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Djuric, S.W., BaMaung, N.Y., Basha, A., Liu, H., Luly, J.R., Madar, D.J., Sciotti, R.J., Tu, N.P., Wagenaar, F.L., Wiedeman, P.E., Zhou, X., Ballaron, S., Bauch, J., Chen, Y.W., Chiou, X.G., Fey, T., Gauvin, D., Gubbins, E., Hsieh, G.C., Marsh, K.C., Mollison, K.W., Pong, M., Shaughnessy, T.K., Sheets, M.P., Smith, M., Trevillyan, J.M., Warrior, U., Wegner, C.D., and Carter, G.W., 3,5-Bis(trifluoromethyl)pyrazoles: a novel class of NFAT transcription factor regulator, J. Med. Chem., 2000, vol. 43, p. 2975.

    Article  CAS  PubMed  Google Scholar 

  14. Feske, St., CRAC channels and disease—from human CRAC channelopathies and animal models to novel drugs, Cell Calcium, 2019, vol. 80, p. 112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gao, R., Gao, X., Xiaa, J., Tiana, Y., Barretta, J.E., Daib, Y., and Hu, H., Potent analgesic effects of a store-o-perated calcium channel inhibitor, Pain, 2013, vol. 154, p. 2034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gao, X.H., Gao, R., Tian, Y.Z., McGonigle, P., Barrett, J.E., Dai, Y., and Hu, H., A Store-operated calcium channel inhibitor attenuates collagen-induced arthritis, Br. J. Pharmacol., 2015, vol. 172, p. 2991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Goeger, D.E., Riley, R.T., Dorner, J.W., and Cole, R.J., Cyclopiazonic acid inhibition of the Ca2+ transport ATPase in rat skeletal muscle sarcoplasmic reticulum vesicles, Biochem. Pharmacol., 1988, vol. 37, p. 978.

    Article  CAS  PubMed  Google Scholar 

  18. Grynkiewicz, G., Poenie, M., and Tsien, R.Y., A new ge-neration of Ca2+ indicators with greatly improved fluorescence properties, J. Biol. Chem., 1985, vol. 260, p. 3440.

    Article  CAS  PubMed  Google Scholar 

  19. He, L.-P., Hewavitharana, T., Soboloff, J., Spas-sova, M.A., and Gill, D.L., A functional link between store-operated and TRPC channels revealed by the 3,5-bis(trifluoromethyl)pyrazole derivative, BTP2, J. Biol. Chem., 2005, vol. 280, p. 10997.

    Article  CAS  PubMed  Google Scholar 

  20. Ishikawa, J., Ohga, K., Yoshino, T., Takezawa, R., Ichikawa, A., Kubota, H., and Yamada, T., A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes, J. Immunol., 2003, vol. 170, p. 4441.

    Article  CAS  PubMed  Google Scholar 

  21. Jairaman, A. and Prakriya, M., Molecular pharmacology of store-operated CRAC channels, Channels, 2013, vol. 7, p. 402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kimura, M., Nishi, K., Higashikawa, A., Ohyama, S., Sakurai, K., Tazaki, M., and Shibukawa, Y., High pH-sensitive store-operated Ca2+ entry mediated by Ca2+ release-activated Ca2+ channels in rat odontoblasts, Front. Physiol., 2018, vol. 9, p. 443. https://doi.org/10.3389/fphys.2018.00443

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kurilova, L.S., Krutetskaya, Z.I., Lebedev, O.E., Krutetskaya, N.I., and Antonov, V.G., The effect of oxidized glutathione and its pharmacological analogue glutoxim on i-ntracellular Ca2+ concentration in macrophages, Cell Tissue Biol., 2008, vol. 2, p. 322.

    Article  Google Scholar 

  24. Kurilova, L.S., Krutetskaya, Z.I., Lebedev, O.E., Krutetskaya, N.I., and Antonov, V.G., The involvement of actin cytoskeleton in glutoxim and molixan effect on intracellular Ca2+ concentration in macrophages, Cell Tissue Biol., 2012, vol. 6, no. 3, p. 240.

    Article  Google Scholar 

  25. Lacruz, R.S. and Feske, St., Diseases caused by mutations in ORAI1 and STIM1, Ann. N.Y. Acad. Sci., 2015, vol. 1356, p. 45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Law, M., Morales, J.L., Mottram, L.F., Iyer, A., Peterson, B.R., and August, A., Structural requirements for the inhibition of calcium mobilization and mast cell activation by the pyrazole derivative BTP2, J. Biochem. Cell Biol., 2011, vol. 43, p. 1228.

    Article  CAS  Google Scholar 

  27. Lewis, R.S., Store-operated calcium channels: from function to structure and back again, Cold Spring Harb. Perspect. Biol., 2020, vol. 12, no. 5. https://doi.org/10.1101/cshperspect.a035055

  28. Liu, S., Hasegawa, H., Takemasa, E., Suzuki, Y., Oka, K., Kiyoi, T., Takeda, H., Ogasawara, T., Sawasaki, T., Yasukawa, M., and Maeyama, K., Efficiency and safety of CRAC inhibitors in human rheumatoid arthritis xenograft models, J. Immunol., 2017, vol. 199, p. 1584.

    Article  CAS  PubMed  Google Scholar 

  29. Lunz, V., Romanin, C., and Frischauf, I., STIM1 activation of Orai1, Cell Calcium, 2019, vol. 77, p. 29.

    Article  CAS  PubMed  Google Scholar 

  30. Miyoshi, M., Liu, Sh., Morizane, A., Takemasa, E., Suzuki, Y., Kiyoi, T., Maeyama, K., and Mogi, M., Efficacy of constant long-term delivery of YM-58483 for the treatment of rheumatoid arthritis, Eur. J. Pharmacol., 2018, vol. 824, p. 89.

    Article  CAS  PubMed  Google Scholar 

  31. Monahan, R.A., Dvorak, H.F., and Dvorak, A.M., Ultrastructural localization of nonspecific esterase activity in guinea pig and human monocytes, macrophages and lymphocytes, Blood, 1981, vol. 58, p. 1089.

    Article  CAS  PubMed  Google Scholar 

  32. Moreno, C. and Vaca, L., Microdomain organization of SOCE signaling, in Store-Operated Ca 2+ Entry (SOCE) Pathways. Wien: Springer-Verlag, 2012, p. 93.

    Google Scholar 

  33. Nguyen, N.T., Han, W., Cao, W.-M., Wang, Y., Wen, S., Huang, Y., Li, M., Du, L., and Zhou, Y., Store-operated calcium entry mediated by ORAI and STIM, Compr. Phys-iol., 2018, vol. 8, p. 981.

    Article  Google Scholar 

  34. Nurbaeva, M.K., Eckstein, M., Snead, M.L., Feske, S., and Lacruz, R.S., Store-operated Ca2+ entry modulates the expression of enamel genes, J. Dent. Res., 2015, vol. 94, p. 1471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nwokonko, R.M., Cai, X., Loktionova, N.A., Wang, Y., Zhou, Y., and Gill, D.L., The STIM-Orai pathway: conformational coupling between STIM and Orai in the activation of store-operated Ca2+ entry, Adv. Exp. Med. Biol., 2017, vol. 993, p. 83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Prakriya, M. and Lewis, R.S., Store-operated calcium channels, Physiol. Rev., 2015, vol. 95, p. 1383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Putney, J.W., Capacitative calcium entry revisited, Cell Calcium, 1990, vol. 11, p. 611.

    Article  CAS  PubMed  Google Scholar 

  38. Putney, J.W., Pharmacology of capacitative calcium entry, Mol. Interv., 2001, vol. 1, p. 84.

    CAS  PubMed  Google Scholar 

  39. Putney, J.W., Pharmacology of store-operated calcium channels, Mol. Interv., 2010, vol. 10, p. 209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Putney, J.W., The physiological function of store-operated calcium entry, Neurochem. Res., 2011, vol. 36, p. 1157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Putney, J.W., Store-operated calcium entry: an historical overview, Adv. Exp. Med. Biol., 2017, vol. 981, p. 205.

    Article  CAS  PubMed  Google Scholar 

  42. Rahman, S. and Rahman, T., Unveiling some FDA-approved drugs as inhibitors of the store-operated Ca2+ entry pathway, Sci. Rep., 2017, vol. 7, p. 12881. https://doi.org/10.1038/s41598-017-13343-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Randriamampita, C. and Trautmann, A., Ionic channels in murine macrophages, Cell. Biol., 1987, vol. 105, p. 761.

    Article  CAS  Google Scholar 

  44. Sabourin, J., Gal, L.L., Saurwein, L., Haefliger, J.-A., Raddatz, E., and Allagnat, F., Store-operated Ca2+ entry mediated by Orai1 and TRPC1 participates to insulin secretion in rat beta-cells, J. Biol. Chem., 2015, vol. 290, p. 30530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sadaghiani, A.M., Lee, S.M., Odegaard, J.I., Leveson-Gower, D.B., McPherson, O.M., Novick, P., Kim, M.R., Koehler, A.N., Negrin, R., Dolmetsch, R.E., and Park, Ch.Y., Identification of Orai1 channel inhibitors by using minimal functional domains to screen small molecule microarrays, Chem. Biol., 2014, vol. 21, p. 1278.

    Article  CAS  PubMed  Google Scholar 

  46. Shaw, P.J. and Feske, St., Physiological and pathophysiological functions of SOCE in the immune system, Front. Biosci., 2013, vol. 4, p. 2253.

    Google Scholar 

  47. Sokolova, G.B., Sinitsyn, M.V., Kozhemiakin, L.A., and Perel’man, M.I., Glutoxim in the complex treatment of tuberculosis, Antibiot. Khimioter., 2002, vol. 2, p. 20.

    Google Scholar 

  48. Stauderman, K.A., CRAC channels as targets for drug discovery and development, Cell Calcium, 2018, vol. 74, p. 147.

    Article  CAS  PubMed  Google Scholar 

  49. Sweeney, Z.K., Minatti, A., Button, D.C., and Patrick, S., Small-molecule inhibitors of store-operated calcium entry, Chem. Med. Chem., 2009, vol. 4, p. 706.

    Article  CAS  PubMed  Google Scholar 

  50. Takezawa, R., Cheng, H., Beck, A., Ishikawa, J., Launay, P., Kubota, H., Kinet, J.P., Fleig, A., Yamada, T., and Penner, R., A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity, Mol. Pharmacol., 2006, vol. 69, p. 1413.

    Article  CAS  PubMed  Google Scholar 

  51. Thastrup, O., Dawson, A.P., Scharff, O., Foder, B., Cullen, P.J., Drobak, B.K., Bjerrum, P.J., Christensen, S.B., and Hanley, M.R., Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage, Agents Actions, 1989, vol. 27, p. 17.

    Article  CAS  PubMed  Google Scholar 

  52. Tian, Ch., Du, L., Zhou, Y., and Li, M., Store-operated CRAC channel inhibitors: opportunities and challenges, Future Med. Chem., 2016, vol. 8, p. 817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tolstoi, O.A., Tsygan, V.N., Klimov, A.G., Stepanov, A.V., and Antushevich, A.E., Experimental evaluation of the efficiency of the drug molixan on restoring the operation of virus-infected laboratory animals, Vestn. Ross. Voenno-Med. Akad., 2019, vol. 38, no. 1, p. 271.

    Google Scholar 

  54. Trebak, M. and Kinet, J.-P., Calcium signalling in T cells, Nat. Rev. Immunol., 2019, vol. 19, p. 154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Trevillyan, J.M., Chiou, X.G., Chen, Y.W., Ballaron, S.J., Sheets, M.P., Smith, M.L., Wiedeman, P.E., Warrior, U., Wilkins, J., Gubbins, E.J., Gagne, G.D., Fagerland, J., Carter, G.W., Luly, J.R., Mollison, K.W., and Djuric, S.W., Potent inhibition of NFAT activation and T cell cytokine production by novel low molecular weight pyrazole compounds, J. Biol. Chem., 2001, vol. 276, p. 48118.

    Article  CAS  PubMed  Google Scholar 

  56. Vaca, L., SOCIC: the store-operated calcium influx complex, Cell Calcium, 2010, vol. 47, p. 199.

    Article  CAS  PubMed  Google Scholar 

  57. Vaeth, M. and Feske, S., Ion channelopathies of the immune system, Curr. Opin. Immunol., 2018, vol. 52, p. 39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Vig, M. and Kinet, J.-P., Calcium signaling in immune cells, Nat. Immunol., 2009, vol. 10, p. 21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Waldron, R.T., Chen, Y., Pham, H., Go, A., Su, H.-Y., Hu, Ch., Wen, L., Husain, S.Z., Sugar, C.A., Roos, J., Ramos, S., Lugea, A., Dunn, M., Stauderman, K., and Pandol, S.J., The Orai Ca2+ channel inhibitor CM4620 targets both parenchymal and immune cells to reduce inflammation in experimental acute pancreatitis, J. Physiol., 2019, vol. 597.12, p. 3085.

    Article  CAS  Google Scholar 

  60. Wei, D., Mei, Y., Xia, J., and Hu, H., Orai1 and Orai3 mediate store-operated calcium entry contributing to neuronal excitability in dorsal root ganglion neurons, Front. Cell. Neurosci., 2017, vol. 11, p. 400. https://doi.org/10.3389/fncel.2017.00400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Xia, J., Pan, R., Gao, X., Meucci, O., and Hu, H., Native store-operated calcium channels are functionally expressed in mouse spinal cord dorsal horn neurons and regulate res-ting calcium homeostasis, J. Physiol., 2014, vol. 592.16, p. 3443.

    Article  CAS  Google Scholar 

  62. Xie, Q., Zhang, Y., Zhai, C., and Bonanno, J.A., Calcium influx factor from cytochrome P-450 metabolism and secretion-like coupling mechanisms for capacitative calcium entry in corneal endothelial cells, J. Biol. Chem., 2002, vol. 277, p. 16559.

    Article  CAS  PubMed  Google Scholar 

  63. Zeng, B., Chen, G.-L., Garcia-Vaz, E., Bhandari, S., Daskoulidou, N., Berglund, L.M., Jiang, H., Hallett, T., Zhou, L.-P., Huang, L., Xu, Z.-H., Nair, V., Nelson, R.G., Ju, W., Kretzler, M., Atkin, S.L., Gomez, M.F., and Xu, Sh.-Z., ORAI channels are critical for receptor-mediated endocytosis of albumin, Nat. Commun., 2017, vol. 8, p. 1920. https://doi.org/10.1038/s41467-017-02094-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zitt, C., Strauss, B., Schwarz, E.C., Spaeth, N., Rast, G., Hatzelmann, A., and Hoth, M., Potent inhibition of Ca2+-release-activated Ca2+ channels and T-lymphocyte activation by the pyrazole derivative BTP2, J. Biol. Chem., 2004, vol. 279, p. 12427.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was carried out within the framework of the research program of the Department of Biophysics, St. Petersburg State University, and the Department of Clinical Biochemistry and Laboratory Diagnostics, Kirov Military Medical Academy (St. Petersburg), as well as St. Petersburg State University agreements for the performance of research work no. 28-12-38 of March 5, 2018, and 05/03-20 of March 12, 2020.

Author information

Authors and Affiliations

  1. Department of Biophysics, St. Petersburg State University, 199034, St. Petersburg, Russia

    L. S. Milenina, Z. I. Krutetskaya & N. I. Krutetskaya

  2. Department of Clinical Biochemistry and Laboratory Diagnostics, Kirov Military Medical Academy, 194044, St. Petersburg, Russia

    V. G. Antonov

Authors
  1. L. S. Milenina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z. I. Krutetskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. G. Antonov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. I. Krutetskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to L. S. Milenina or Z. I. Krutetskaya.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of int-erest.

Statement on the welfare of animals. Experiments on animals were carried out in accordance with the generally accepted International Guiding Principles for Biomedical Research Involving Animals (1985) and the requirements of the Order of the Ministry of Health of the Russian Federation no. 267 dated June 19, 2003, “On the Approval of the Rules of Laboratory Practice in the Russian Federation.”

Additional information

Translated by I. Fridlyanskaya

Abbreviations: [Ca2+]i—intracellular concentration of Ca2+; CPA—cyclopiazonic acid.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Milenina, L.S., Krutetskaya, Z.I., Antonov, V.G. et al. Pyrazole Derivative Attenuates Store-Dependent Ca2+ Entry in Rat Peritoneal Macrophages. Cell Tiss. Biol. 15, 293–300 (2021). https://doi.org/10.1134/S1990519X21030068

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990519X21030068

Keywords:

Search

Navigation