Modulation of myometrium contractive activity and intracellular Са2 homeostasis by calix4arene С-1130 selective inhibitor of the sodium pump
O. Tsymbalyuk
, T. Veklich
, R. Rodik
, O. Maliuk
, S. Karakhim
, V. Kalchenko
, S. Kosterin
Abstract: Objective: Na+,K+-ATPase of the plasma membrane plays an important role in maintaining the excitability of smooth muscle cells; directed modulation of the activity of this enzyme can be used to normalize the tone and contractility of muscle tissue. Materials and methods: The cone-like dioctyloxycalix[4]arene C-1130, containing two bioaffine formations of (2-pyridyl)methylaminophosphonic acid on the upper rim of the macrocycle, was syn-thesized. The methods of enzymatic and kinetic analysis were used for the study of the AТР-hydrolase activities in plasma membranes of the rat myometrium cells. Determining the changes in the concentration of intracellular Са2+ was studied with confocal microscopy. The study of the spontaneous contractive activity (registered in the isomet-ric and isotonic modes) in muscle preparations was conducted according to the method of complex mechanokinetic analysis. Results: Calix[4]arene С-1130 had an efficient inhibitory effect on Na+, K+-ATPase activity in the plasma membrane of myocytes (І0.5 = 38 ± 6 nM), and had no effect on other ATPases. С-1130 (10 µM) conditioned the increase in the intracellular concentration of Са ions in the myocytes and activated the spontaneous contractive activity of rat myometrium. This calix[4]arene changed time, force, and velocity parameters of isometric and iso-tonic spontaneous contractions. Under the preliminary effect of ouabain, C-1130 did not change any mechanoki-netic parameter of spontaneous contractions. Discussion: Calix[4]arene С-1130 only blocked Na+,К+-ATPase of the plasma membrane without affecting other proteins, involved in the processes of myometrium contraction-relaxation. Conclusion: Calix[4]arene С-1130, a selective inhibitor of Nа+, К+-ATPase, may be relevant for the creation of medicines and for the pharmacological researches.
Series on Biomechanics, Vol.38, No.1 (2024), 71-89
DOI: 10.7546/SB.08.01.2024
Keywords: calix4arenes; contrac-tion; mechanokinetics; myometrium; Nа; plasma membrane; smooth muscle cells; К-ATPase
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| Date published: 2024-04-23
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