T. O. Veklich¹, R. D. Labyntseva¹, O. A. Shkrabak¹, O. V. Tsymbalyuk²,
R. V. Rodik³, V. I. Kalchenko³, S. O. Kosterin¹

¹Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
²Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
³Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: veklich@biochem.kiev.ua; otsymbal@bigmir.net; manli@ioch.kiev.ua

Received: 04 Jule 2019; Accepted: 29 November 2019

The discovery of compounds that might modify myometrial contractility is an important area of researches. In our previous experiments, we found that some representatives of macrocyclic compounds fami­ly – calix[4]arenes – can modify the enzymatic and transport activity of membrane-bound cation-transport ATP hydrolases. The aim of this work was to study and compare the effect of calix[4]arene C-107 on the enzymatic activities of Mg²⁺-dependent ATPases of the uterine smooth muscle, namely: ouabain-sensitive Na⁺,K⁺-ATPase, plasma membrane Ca²⁺-independent “basal” Mg²⁺-ATPase, ATPase of the actomyosin complex and myosin subfragment-1, with effect on the contractile activity of the myometrium. It was shown that calix[4]arene C-107 efficiently inhibited myometrium Na⁺,K⁺-ATPase (I₅₀ = 54 ± 6 nM) selectively to other ATP-hydrolases of the plasma membrane and simultaneously activated the enzymatic activity of the myosin ATPase of smooth muscles (A₅₀ = 9.6 ± 0.7 μM). Such reciprocal biochemical effects led to the stimulation of the smooth muscle contractile activity that was demonstrated by the tensometric method using different isolated smooth muscles. Calix[4]arene С-107 was shown to stimulate the increase of the tonic component of myometrium contractions induced by oxytocin, as well as contractions of the caecum muscles induced by high-potassium solution or acetylcholine, and to maintain increased tension for a long time. Thus, calix[4]arene C-107 is a prospective compound for enhancing the smooth muscle basal tone and/or contraction in case of hypotonic dysfunctions.