Ukr.Biochem.J. 2023; Volume 95, Issue 6, Nov-Dec, pp. 5-20

doi: https://doi.org/10.15407/ubj95.06.005

Thiacalix[4]arene С-1087 is the selective inhibitor of the calcium pump of smooth muscle cells plasma membrane

Т. О. Veklich1*, R. V. Rodik2, О. V. Tsymbalyuk3,
О. V. Shkrabak1, O. V. Maliuk1, S. O. Karakhim1,
S. H. Vyshnevskyi3, V. І. Kalchenko3, S. O. Kosterin1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: veklich@biochem.kiev.ua;
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
3Educational and Scientific Institute of High Technologies,
Taras Shevchenko National University of Kyiv, Kyiv, Ukraine;

Received: 01 September 2023; Revised: 23 October 2023;
Accepted: 01 December 2023; Available on-line: 18 December 2023

The enzymatic and kinetic analyses were used to demonstrate that 5,11,17,23-tetra(trifluoro)methyl(phenylsulfonylimino)methylamino-25,27-dihexyloxy-26,28-dihydroxythiacalix[4]arene С-1087 effectively inhibited the Са2+,Mg2+-АТРase activity of the rat myometrium cells plasma membrane (І0.5 = 9.4 ± 0.6 µM) with no effect on the relative activity of other membrane ATPases. With the use of confocal microscopy and Ca2+-sensitive fluorescent probe fluo-4, it was shown that the application of thiacalix[4]arene С-1087 to the immobilized uterus myocytes increased the cytosolic concentration of Ca2+. Tenzometric studies of rat uterus smooth muscles with the subsequent mechanokinetic analysis revealed that thiacalix[4]arene С-1087 considerably decreased the maximal velocity of the relaxation of both spontaneous contractile response and contraction induced by hyperpotassium solution.

Keywords: , , , , ,


References:

  1. Wray S. Insights from physiology into myometrial function and dysfunction. Exp Physiol. 2015;100(12):1468-1476. PubMed, CrossRef
  2. Kosterin SO, Babich LG, Shlykov SG, Danylovych IuV, Veklich ТО, Mazur YuYu. Biochemical properties and regulation of smooth muscle cell Са2+-transporting systems. K.: Science opinion, 2016. 210 р.
  3. Noble D, Herchuelz A. Role of Na/Ca exchange and the plasma membrane Ca2+-ATPase in cell function. EMBO Rep. 2007;8(3):228-232. PubMed, PubMedCentral, CrossRef
  4. Futai M, Wada Y, Kaplan J. Catalytic and transport mechanism of the sarco-(endo)plasmic reticulum Ca2+-ATPase (SERCA). Handbook of ATPases: biochemistry, cell biology, pathophysiology. Ed. John Wiley & Sons. – Weinheim: Wiley-VCH, 2004; 63-84.
  5. Karaki H, Ozaki H, Hori M, Mitsui-Saito M, Amano K, Harada K, Miyamoto S, Nakazawa H, Won KJ, Sato K. Calcium movements, distribution, and functions in smooth muscle. Pharmacol Rev. 1997;49(2):157-230. PubMed
  6. Brini M, Carafoli E. The plasma membrane Ca2+ ATPase and the plasma membrane sodium calcium exchanger cooperate in the regulation of cell calcium. Cold Spring Harb Perspect Biol. 2011;3(2):a004168. PubMed, PubMedCentral, CrossRef
  7. Sanborn BM. Hormonal signaling and signal pathway crosstalk in the control of myometrial calcium dynamics. Semin Cell Dev Biol. 2007;18(3):305-314. PubMed, PubMedCentral, CrossRef
  8. Penniston JT, Enyedi A. Modulation of the plasma membrane Ca2+ pump. J Membr Biol. 1998;165(2):101-109. PubMed, CrossRef
  9. Liu L, Ishida Y, Okunade G, Shull GE, Paul RJ. Role of plasma membrane Ca2+-ATPase in contraction-relaxation processes of the bladder: evidence from PMCA gene-ablated mice. Am J Physiol Cell Physiol. 2006;290(4):C1239-C1247. PubMed, CrossRef
  10.  Cartwright EJ, Oceandy D, Austin C, Neyses L. Ca2+ signalling in cardiovascular disease: the role of the plasma membrane calcium pumps. Sci China Life Sci. 2011;54(8):691-698. PubMed, CrossRef
  11. Brini M. Plasma membrane Ca(2+)-ATPase: from a housekeeping function to a versatile signaling role. Pflugers Arch. 2009;457(3):657-664. PubMed, CrossRef
  12. Liu L, Ishida Y, Okunade G, Pyne-Geithman GJ, Shull GE, Paul RJ. Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice. Am J Physiol Cell Physiol. 2007;292(1):C423-C431. PubMed, CrossRef
  13. Uterine contractility. Ed. by R.E. Garfield – Serano Symposia, VSA, Norwell, Massachusetts, 1990. 388 p.
  14. Hertelendy F, Zakar T. Regulation of myometrial smooth muscle functions. Curr Pharm Des. 2004;10(20):2499-2517. PubMed, CrossRef
  15. Calixarenes in the Nanoworld. Ed. by Vicens J, Harrowfield J, Baklouti L. Springer, Dordrecht, The Netherlands, 2007. 395 p. CrossRef
  16. Calixarenes and Beyond. Ed. by Neri P, Sessler JL, Wang MX. Springer International Publishing, Switzerland, 2016. 1062 p. CrossRef
  17. Español ES, Villamil MM. Calixarenes: Generalities and Their Role in Improving the Solubility, Biocompatibility, Stability, Bioavailability, Detection, and Transport of Biomolecules. Biomolecules. 2019;9(3):90. PubMed, PubMedCentral, CrossRef
  18. Rodik RV, Boyko VI, Kalchenko VI. Calixarenes in biotechnology and bio-medical researches. Front Med Chem. Eds. Atta-ur-Rahman, Choudhary MI, Reitz AB. Bentham Science Publishers. 2016;8:206–301. CrossRef
  19. Pan YC, Hu XY, Guo DS. Biomedical Applications of Calixarenes: State of the Art and Perspectives. Angew Chem Int Ed Engl. 2021;60(6):2768-2794. PubMed, CrossRef
  20. Fan X, Guo X. Development of calixarene-based drug nanocarriers. J Mol Liquids. 2021;325:115246. CrossRef
  21. Coleman AW, Jebors S, Cecillon S, Perret P, Garin D, Marti-Battle D, Moulin M. Toxicity and biodistribution of para-sulfonato-calix[4]arene in mice. New J Chem. 2008;32:780-782. CrossRef
  22. Kosterin SO, Kalchenko VI, Veklich ТО, Babich LG, Shlykov SG. Calixarenes as modulators of ATP-hydrilizing systems of smooth muscles. K.: Science opinion, 2019. 256 р.
  23. Rassukana YV, Onys’ko PP, Grechukha AG, Sinitsa AD. N-(Arylsulfonyl)trihaloacetimidoyl Chlorides and Their Reactions with Phosphites. Eur J Org Chem. 2003;2003(21):4181-4186. CrossRef
  24. Veklich ТО, Kosterin SO. Comparative study of properties of Na+, K+-ATPase and Mg2+-ATPase of the myometrium plasma membrane. Ukr Biokhim Zhurn. 2005;77(2):66-75. (In Ukrainian). PubMed
  25. Kondratiuk ТP, Bychenok SF, Prishchepa АА, Babich LG, Kurskiy MD. Isolation and characteristics of the plasma membrane fraction from the swine myometrium. Ukr Biokhim Zhurn. 1986;58(4):50-56. (In Russian). PubMed
  26. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1-2):248-254. PubMed, CrossRef
  27. Mollard P, Mironneau J, Amedee T, Mironneau C. Electrophysiological characterization of single pregnant rat myometrial cells in short-term primary culture. Am J Physiol. 1986;250(1):C47-C54. PubMed, CrossRef
  28. Rathbun WB, Betlach MV. Estimation of enzymically produced orthophosphate in the presence of cysteine and adenosine triphosphate. Anal Biochem. 1969;28(1):436-445. PubMed, CrossRef
  29. Veklich TO, Shkrabak OA, Nikonishyna YuV, Rodik RV, Kalchenko VI, Kosterin SO. Calix[4]arene С-956 selectively inhibits plasma membrane Са(2+),Mg(2+)-АТРase in myometrial cells. Ukr Biochem J. 2018;90(5):34-42. CrossRef
  30. Magocsi M, Penniston JT. Ca2+ or Mg2+ nucleotide phosphohydrolases in myometrium: two ecto-enzymes. Biochim Biophys Acta. 1991;1070(1):163-172. PubMed, CrossRef
  31. Amédée T, Mironneau C, Mironneau J. Isolation and contractile responses of single pregnant rat myometrial cells in short-term primary culture and the effects of pharmacological and electrical stimuli. Br J Pharmacol. 1986;88(4):873-880. PubMed, PubMedCentral, CrossRef
  32. Kosterin S, Tsymbalyuk O, Holden O. Multiparameter analysis of mechanokinetics of the contractile response of visceral smooth muscles. Series on Biomechanics. 2021;35(1):14-30. Burdyga TV, Kosterin SA. Kinetic analysis of smooth muscle relaxation. Gen Physiol Biophys. 1991;10(6):589-598. PubMed
  33. Burdyga TV, Kosterin SA. Kinetic analysis of smooth muscle relaxation. Gen Physiol Biophys. 1991;10(6):589-598. PubMed
  34. Iki N, Narumi F, Fujimoto T, Morohashi N, Miyano S. Selective synthesis of three conformational isomers of  tetrakis[(ethoxycarbonyl)methoxy]thiacalix[4]arene and their complexation properties towards alkali metal ions. J Chem Soc Perkin Trans 2. 1998;(12):2745-2750. CrossRef
  35. Lang J, Dvořáková H, Bartošová I, Lhotak P, Stibor I, Hrabal R. Conformational flexibility of a novel tetraethylether of thiacalix[4]arene. A comparison with the “classical” methylene-bridged compounds. Tetrahedron Lett. 1999;40(2):373-376. CrossRef
  36.  Kasyan O, Healey ER, Drapailo A, Zaworotko M, Cecillon S, Coleman AW, Kalchenko V. Synthesis, Structure and Selective Upper Rim Functionalization of Long Chained Alkoxythiacalix[4]arenes. J Incl Phenom Macrocycl Chem. 2007;58:127–132. CrossRef
  37. Veklich TO, Shkrabak OA, Nikonishyna YuV, Rodik RV, Kalchenko VI, Kosterin SO. Calix[4]arene C-90 as a promising supramolecular compound to regulate the activity of plasma membrane Ca2+,Mg2+-ATPase of smooth muscle cells. Nanosist Nanomater Nanotehnol. 2017;15(2):373-380. (In Ukrainian).
  38. Danylovych IuV, Chunikhin OIu, Danylovich HV. Investigation of the changes in uterine myocytes size depending on contractile activity modulators by photon correlation spectroscopy. Fiziol Zh. 2013;59(1):32-39. (In Ukrainian). PubMed
  39. Tsymbalyuk OV, Kosterin SO. Influence of calixarene С-90 jn contractile activity of rat myometrium smooth muscles. Studia Biologica. 2013;7(3):87-98. CrossRef
  40. symbalyuk OV. Kinetics of relaxation of rat myometrium in conditions of inhibition of plasma membrane calcium pump and systems of active Са2+ transport of intracellular Са2+-depot. Studia Biologica. 2018;12(2):3-12. CrossRef
  41. Ishida Y, Paul RJ. Ca2+ clearance in smooth muscle: lessons from gene-altered mice. J Smooth Muscle Res. 2005;41(5):235-245. PubMed, CrossRef

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