[Spatial structure of the calixarene-aminophosphonic acids is important for their inhibition of the Na+,K(+)-ATPase activity in plasma membrane of smooth muscle cells].

It was found that calixarene C-107 (5,17-diamino(2-pyridyl)methylphosphono-11,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix[4]arene) could effectively reduce Na+,K(+)-ATPase activity of the myometrium cell plasmatic membranes (the value of the apparent constant of inhibition I0.5 was 33 +/- 4 nM) while it practically did not influence the "basal" Mg2(+)-ATPase activity of the same membrane. In comparative experiments, we have shown that the model calixarene C-150--the calixarene "scaffold" (26,28-dihydroxy-25,27-dipropoxycalix[4]arene), and the model compound M-3 (4-hydroxyaniline(2-pyridine)methylphosphonic acid)--a fragment of the calixarene C-107, had practically no influence on the enzymatic activities of Na+,K(+)-ATPase and Mg(2+)-ATPase over a wide range of concentrations. Hence, the influence of calixarene C-107 on Na+,K(+)-ATPase activity was caused by the joint action of two aminophosphonic substituents on the upper rim of the calixarene bowl. The isomer of calixarene C-107--calixarene C-160 (5,11-diamino(2-pyridyl)methylphosphono-17,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix[4]arene) also did not influence the Na+,K(+)-ATPase and Mg(2+)-ATPase activities of plasmatic membrane of myometrium cells. We carried out molecular modeling of calixarenes C-107 and C-160 and showed differences in interatomic distance between aminophosphonic substituents of mentioned calixarenes. We came to the conclusion that spatial structure of calixarene C-107, namely localization of two aminophosphonic substituents in 5,17 position of the upper rim of this calixarene, is crucial for inhibition of Na+,K(+)-ATPase activity. Using laser correlation spectroscopy it was found that the 100 microM solution of calixarene C-107 and 2.5% DMSO had microparticles with size range from 100 nm to 10 microm. Plasma membrane vesicles had average hydrodynamic diameter 401 +/- 17 nm, but after interaction of these vesicles with calixarene C-107 we have registered the creation of some particles with sizes greater than 10 microm. Therefore membrane vesicles agglutinated to each other and/ or to calixarene microparticles.