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Inhibitors of the Metabolism of Arachidonic Acid Suppress Ca2+ Responses Induced by Trifluoperazine in Macrophages

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Abstract

The influence of the neuroleptic trifluoperazine on the intracellular concentration of Ca2+ in macrophages of rats was studied using a Fura-2AM fluorescent Ca2+ probe. It was found that trifluoperazine causes a dose-dependent increase in the intracellular Ca2+ concentration associated with Ca2+ mobilization from intracellular Ca2+ stores and subsequent entry of Ca2+ into peritoneal macrophages of rats. It was also shown that inhibitors of phospholipase A2 (4-bromophenacyl bromide, prednisolone, and dexamethasone), cyclooxygenases (aspirin and indomethacin), and lipoxygenases (caffeic acid, zileuton, and baicalein) suppress Ca2+ responses induced by trifluoperazine in macrophages. The data obtained indicate the participation of enzymes and/or products of the cascade of arachidonic acid metabolism in the influence of trifluoperazine on the intracellular concentration of Ca2+ in peritoneal macrophages.

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Abbreviations

AA:

arachidonic acid

4-BPB:

4-bromophenacyl bromide

[Ca2+]i :

intracellular concentration of Ca2+

PLA2 :

phospholipase A2

TFP:

trifluoperazine

References

  • Becker, D.E., Basic and clinical pharmacology of glucocorticosteroids, Anesth. Prog., 2013, vol. 60, pp. 25–32.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brown, G.P., Monick, M.M., and Hunninghake, G.W., Human alveolar macrophage arachidonic acid metabolism, Am. J. Physiol. Cell Physiol., 1988, vol. 254, pp. C809–C815.

    Article  CAS  Google Scholar 

  • 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, pp. 761–771.

    CAS  Google Scholar 

  • Buckley, N.A. and Sanders, P., Cardiovascular adverse effects of antipsychotic drugs, Drug Saf., 2000, vol. 23, pp. 215–228.

    Article  PubMed  CAS  Google Scholar 

  • Chung, T.-W., Moon, S.-K., Chang, Y.-C., Ko, J.-H., Lee, Y.-C., Cho, G., Kim, S.-H., Kim, J.-G., and Kim, C.-H., Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism, J. Fed. Amer. Soc. Exp. Biol., 2004, vol. 18, pp. 1670–1681.

    CAS  Google Scholar 

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

    Google Scholar 

  • De Witt, D.L., El Harish, E.A., Kraemer, S.A., Andrews, M.J., Yao, E.F., Armstrong, R.L., and Smith, W.L., The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases, J. Biol Chem., 1990, vol. 265, pp. 5192–5198.

    Google Scholar 

  • Dilsaver, S.C., Antipsychotic agents: a review, Am. Fam. Phys., 1993, vol. 47, pp. 199–204.

    CAS  Google Scholar 

  • Dubois, R.N., Abramson, S.B., Crofford, L., Gupta, R.A., Simon, L.S., Van de Putte, L.B.A., and Lipsky, P.E., Cyclooxygenase in biology and disease, FASEB J., 1998, vol. 12, pp. 1063–1073.

    Article  PubMed  CAS  Google Scholar 

  • Feldkamp, M.D., O’Donnell, S.E., Yu, L., and Shea, M.A., Allosteric effects of the antipsychotic drug trifluoperazine on energetics of calcium binding by calmodulin, Proteins, 2010, vol. 78, pp. 2265–2282.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gewert, K. and Sundler, R., Dexametazone down-regulates the 85 kDa phospholipase A2 in mouse macrophages and suppresses its activation, Biochem. J., 1995, vol. 307, pp. 499–504.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grynkiewicz, G., Poenie, M., and Tsien, R.Y., A new generation of Ca2+ indicators with greatly improved fluorescence properties, J. Biol. Chem., 1985, vol. 260, pp. 3440–3450.

    PubMed  CAS  Google Scholar 

  • Hadjimitova, V., Bakalova, R., Traykov, T., Ohba, H., and Ribarov, S., Effect of phenothiazines on protein kinase Cand calcium-dependent activation of peritoneal macrophages, Cell Biol. Toxicol., 2003, vol. 19, pp. 3–12.

    Article  PubMed  CAS  Google Scholar 

  • He, Z., Dunker, A.K., Wesson, C.R., and Trumble, W.R., Ca2+-induced folding and aggregation of skeletal muscle sarcoplasmic reticulum calsequestrin. The involvement of the trifluoperazine-binding site, J. Biol. Chem., 1993, vol. 268, pp. 24635–24641.

    PubMed  CAS  Google Scholar 

  • Irvine, R.F., How is the level of free arachidonic acid controlled in mammalian cells?, Biochem. J., 1982, vol. 204, pp. 3–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jaszczyszyn, A., Gasiorowski, K., Swiatek, P., Malinka, W., Cieslik-Boczula, K., Petrus, J., and Czarnik-Matusewicz, B., Chemical structure of phenothiazines and their biological activity, Pharmacol. Rep., 2012, vol. 64, pp. 16–23.

    Article  PubMed  CAS  Google Scholar 

  • Kang, S., Hong, J., Lee, J.M., Moon, H.E., Jeon, B., Choi, J., Yoon, N.A., Paek, S.H., Roh, E.J., Lee, J., and Kang, S.S., Trifluoperazine, a well-known antipsychotic, inhibits glioblastoma invasion by binding to calmodulin, and disinhibiting calcium release channel IP3R, Mol. Cancer Ther., 2017, vol. 16, pp. 217–227.

    Article  PubMed  CAS  Google Scholar 

  • Khan, S.Z., Longland, C.L., and Michelangeli, F., The effects of phenothiazines and other calmodulin antagonists on the sarcoplasmic and endoplasmic reticulum Ca2+ pumps, Biochem. Pharmacol., 2000, vol. 60, pp. 1797–1806.

    Article  PubMed  CAS  Google Scholar 

  • Krutetskaya, Z.I., Lebedev, O.E., Tyushev, V.E., Krutetskaya, N.I., and Roschina, N.G., The effect of tyrosine kinase and tyrosine phosphatase inhibitors on Ca2+ entry induced by ATP and thapsigargin in peritoneal macrophages, Tsitologiia, 1997, vol. 39, no. 2/3, pp. 164–176.

    CAS  Google Scholar 

  • Krutetskaya, Z.I., Milenina, L.S., Naumova, A.A., Butov, S.N., Antonov, V.G., and Nozdrachev, A.D., The effect of chlorpromazine on intracellular Ca2+ concentration in macrophages, Dokl. Biochem. Biophys., 2017, vol. 474, pp. 162–164.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, J.A., Akarasereenont, P., Thiemermann, C., Flower, R.J., and Vane, J.R., Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenases, Proc. Natl. Acad. Sci. U. S. A., 1994, vol. 90, pp. 11693–11697.

    Article  Google Scholar 

  • 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, pp. 1089–1099.

    PubMed  CAS  Google Scholar 

  • Naumova, A.A., Krutetskaya, Z.I., Milenina, L.S., Krutetskaya, N.I., and Butov, S.N., Chlorpromazine induces Ca2+ responses in macrophages, Med. Akad. Zh., 2016, vol. 16, pp. 62–63.

    Google Scholar 

  • Needleman, P., Turk, J., Jacksick, B.A., Morrison, A.R., and Lefkowith, J.B., Arachidonic acid metabolism, Annu. Rev. Biochem., 1986, vol. 55, pp. 69–102.

    Article  PubMed  CAS  Google Scholar 

  • Oruch, R., Pryme, I.F., and Holmsen, H., Effects of psychotropic drugs on the thrombin-induced liberation of arachidonate in human platelets, Saudi Med. J., 2008, vol. 29, pp. 1397–1407.

    PubMed  Google Scholar 

  • Oruch, R., Lund, A., Pryme, I.F., and Holmsen, H., An intercalation mechanism as a mode of action exerted by psychotropic drugs: results of altered phospholipid substrate availabilities in membranes?, J. Chem. Biol., 2010, vol. 3, pp. 67–88.

    Article  PubMed  PubMed Central  Google Scholar 

  • Qin, J., Zima, A.V., Porta, M., Blatter, L.A., and Fill, M., Trifluoperazine: a ryanodine receptor agonist, Pflugers Arch., 2009, vol. 458, pp. 643–651.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Randriamampita, C. and Trautmann, A., Ionic channels in murine macrophages, Cell. Biol., 1987, vol. 105, pp. 761–769.

    Article  CAS  Google Scholar 

  • Sudeshna, G. and Parimal, K., Multiple non-psychiatric effects of phenothiazines: a review, Eur. J. Pharmacol., 2010, vol. 648, pp. 6–14.

    Article  PubMed  CAS  Google Scholar 

  • 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., Thapsigargi, a novel molecular probe for studying intracellular calcium release and storagen, Agents Actions, 1989, vol. 27, pp. 17–23.

    Article  PubMed  CAS  Google Scholar 

  • Van Leyen, K., Kim, H.Y., Lee, S.-R., Jin, G., Arai, K., and Lo, E.H., Baicalein and 12/15-lipoxygenase in the ischemic brain, Stroke, 2006, vol. 37, pp. 3014–3018.

    Article  PubMed  CAS  Google Scholar 

  • Vandonselaar, M., Hickie, R.A., Quail, J.W., and Delbaere, L.T., Trifluoperazine-induced conformational change in Ca2+-calmodulin, Nat. Struct. Biol., 1994, vol. 1, pp. 795–801.

    Article  PubMed  CAS  Google Scholar 

  • Walenga, R.W., Opas, E.E., and Feinstein, M.B., Differential effects of calmodulin antagonists on phospholipases A2 and C in thrombin-stimulated platelets, J. Biol. Chem., 1981, vol. 256, pp. 12523–12528.

    PubMed  CAS  Google Scholar 

  • Wenzel, S.E. and Kamada, A.K., Zileuton—the first 5-lipoxygenase inhibitor for the treatment of asthma, Ann. Pharmacother., 1996, vol. 30, pp. 858–864.

    Article  PubMed  CAS  Google Scholar 

  • 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, pp. 16559–16566.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

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

    L. S. Milenina, Z. I. Krutetskaya, A. A. Naumova, S. N. Butov, N. I. Krutetskaya & V. G. Antonov

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  1. L. S. Milenina
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  2. Z. I. Krutetskaya
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  3. A. A. Naumova
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  4. S. N. Butov
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  5. N. I. Krutetskaya
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  6. V. G. Antonov
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Correspondence to L. S. Milenina.

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Original Russian Text © L.S. Milenina, Z.I. Krutetskaya, A.A. Naumova, S.N. Butov, N.I. Krutetskaya, V.G. Antonov, 2018, published in Tsitologiya, 2018, Vol. 60, No. 2, pp. 116–121.

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Milenina, L.S., Krutetskaya, Z.I., Naumova, A.A. et al. Inhibitors of the Metabolism of Arachidonic Acid Suppress Ca2+ Responses Induced by Trifluoperazine in Macrophages. Cell Tiss. Biol. 12, 315–322 (2018). https://doi.org/10.1134/S1990519X18040065

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  • DOI: https://doi.org/10.1134/S1990519X18040065

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