Using Fura-2AM microfluorimetry it was shown for the first time that 5-lipoxygenase specific inhibitors zileuton and caffeic acid significantly inhibit Ca2+ responses, induced by neuroleptic trifluoperazine, in macrophages. The results suggest the involvement of 5-lipoxygenases and/or products of 5-lipoxygenase pathway of arachidonic acid cascade in the effect of trifluoperazine on intracellular Ca2+ concentration in macrophages.
trifluoperazine, 5-lipoxygenases, macrophages
1. Dilsaver S.C. Antipsychotic agents: A review. Amer. Fam. Phys., 1993, vol. 47, pp. 199-204.
2. Sudeshna G., Parimal K. Multiple non-psychiatric effects of phenothiazines: a review. Europ. J. Pharmacol., 2010, vol. 648, pp. 6-14.
3. Oruch R., Lund A., Pryme I.F., 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.
4. Jaszczyszyn A., Gasiorowski K., Swiatek P., Malinka W., Cieslik-Boczula K., Petrus J., Czarnik-Matusewicz B. Chemical structure of phenothiazines and their biological activity. Pharmacol. Rep., 2012, vol. 64, pp. 16-23.
5. Feldkamp M.D., O’Donnell S.E., Yu L., Shea M.A. Allosteric effects of the anti-psychotic drug trifluoperazine on energetics of calcium binding by calmodulin. Proteins, 2010, vol. 78, pp. 2265- 2282.
6. Hadjimitova V., Bakalova R., Traykov T., Ohba H., Ribarov S. Effect of phenothiazines on protein kinase C- and calcium-dependent activation of peritoneal macrophages. Cell Biol. Toxicol., 2003, vol., 19, pp. 3-12.
7. Milenina L.S., Kruteckaya Z.I., Naumova A.A., Kruteckaya N.I., Butov S.N., Antonov V.G. Vliyanie trufluoperazina na vnutrikletochnuyu koncentraciyu Sa2+ v makrofagah. Receptory i vnutrikletochnaya signalizaciya, 2017, c. 188-192. [Milenina L.S., Krutetskaya Z.I., Naumova A.A., Krutetskaya N.I., Butov S.N., Antonov V.G. The influence of trifluoperazine on intracellular Ca2+ concentration in macrophages. In: Receptors and intracellular signalling, 2017, pp. 188-192 (in Rus)]
8. Oruch R., Pryme I.F., 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.
9. Walenga R.W., Opas E.E., 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.
10. Kuhn H., Banthiya S., van Leyen K. Mammalian lipoxygenases and their biological relevance. Biochim. Biophys. Acta, 2015, vol. 1851, pp. 308-330.
11. Chung T.-W., Moon S.-K., Chang Y.-C., Ko J.-H., Lee Y.-C., Cho G., Kim S.-H., Kim J.-G., 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.
12. Wenzel S.E., Kamada A.K. Zileuton - the first 5-lipoxygenase inhibitor for the treatment of asthma. Ann. Pharmacother., 1996, vol. 30, pp. 858-864.
13. Milenina L.S., Kruteckaya Z.I., Naumova A.A., Kruteckaya N.I., Butov S.N., Antonov V.G. Arp 2/3-kompleks uchastvuet v deystvii glutoksima i moliksana na vnutrikletochnuyu koncentraciyu Sa2+ v makrofagah. Biofizika, 2014, t. 59, vyp. 5, s. 907-912. [Milenina L.S., Krutetskaya Z.I., Naumova A.A., Krutetskaya N.I., Butov S.N., Antonov V.G. Arp 2/3-complex is involved in the effect of glutoxim and molixan on intracellular Ca2+ concentration in macrophages. Biophysica, 2014, vol. 59, pp. 907-912 (in Rus.)]
14. Grynkiewicz G., Poenie M., Tsien R.Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem., 1985, vol. 260, pp. 3440-3450.
15. Xie Q., Zhang Y., Zhai C., Bonanno J.A. Calcium influx factor from cutochrome 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.
