Mazur I. Calix[4]arene as selective inhibitor of myometrium Mg2+,АТР-dependent plasma membrane calcium pump

It is demonstrated that calix[4]arene C-90 selectively (at the plasma membrane level) inhibits enzymatic and transport activity of Са2+,Mg2+-АТРase (inhibition coefficient І0,5 = 20 mkM). Comparison of C-90 structure analogs determined that quantity and spatial location of sulfonylamide groups on the upper rim of macrocycle plays the main role in inhibition efficiency. Calix[4]arene hydrophobicity directly correlates with inhibition efficiency. Given a negative potential (Gibbs-Donnan model) on the plasma membrane vesicle internal surface ("inside out"), a transport activity of Са2+,Mg2+-АТРase is stimulated, and also C-90 is characterized by a more prominent inhibitory action. On the cellular level calix[4]arene C-90 specific inhibition of plasma membrane Са2+-pump activity leads to an increase of Са2+ intercellular concentration, which was shown using mathematic modelling and laser scanning confocal microscopy. During in vitro experiments calix[4]arene C-90 (10 mkM) was decelerating mechanical tension relaxation in the case of spontaneus myometrium contraction. It also was amplifying the speed of contractions induced by oxytocin (100 nM).