Veklich T O, Shkrabak O A, Mazur Iu Iu, Rodik R V, Boĭko V I, Kal'chenko V I, Kosterin S O
Ukr Biokhim Zh (1999). 2013 Jul-Aug;85(4):20-9.
Plasma membrane Ca2+,Mg2+-ATPase is an important element of general myometrium tonus control mechanism, which also makes a contribution to muscle tension relaxation after its contraction. Expiriments were done on the myometrial cell plasma membrane suspension, which was treated with 0.1% digitonin solution. The authors have investigated the inhibitory action of calix[4]arene C-90 (5,11,17,23-tetra(trifluor) methyl(phenylsulphonylimino)-methylamino-25,26,27,28-tetra propoxi-calix[4]arene) on the Ca2+,Mg2+-ATPase activity (the magnitude of 10.5 was 20.2 +/- 0.5 mkM). The inhibitory action of calix[4]arene C-90 on the activity of Ca2+, Mg2+-ATPase is explained as cooperative action of four trifluormethyl(phenylsulfonylimino)methylamino groups that are spatially oriented on the calix[4]-arene base rather than with the action of tetra-phenol macrocycle or separate pharmacophore sulphonilamidin groups. Considering established kinetic pattern of calix[4]arene C-90 inhibitory action on the plasma membrane Ca2+,Mg2+-ATPase activity, stationary kinetical model of basal calcium concentration control in unexcited uterus myocytes was developed. It is assumed that obtained results may be promising for creation of new generation ("supramolecular") pharmacological agent - uterus basal tonus stimulator - on the base of calix[4] arene C-90.
质膜Ca2 +,Mg2 + -ATP酶是子宫肌层总体张力控制机制的重要组成部分,它在子宫肌层收缩后也有助于肌肉张力的松弛。实验是在子宫肌层细胞质膜悬浮液上进行的,该悬浮液用0.1%的洋地黄皂苷溶液处理。作者研究了杯[4]芳烃C - 90(5,11,17,23 - 四(三氟)甲基(苯磺酰亚氨基)-甲基氨基-25,26,27,28 - 四丙氧基杯[4]芳烃)对Ca2 +,Mg2 + -ATP酶活性的抑制作用(浓度为10.5时为20.2±0.5 mkM)。杯[4]芳烃C - 90对Ca2 +,Mg2 + -ATP酶活性的抑制作用被解释为四个三氟甲基(苯磺酰亚氨基)甲基氨基基团在杯[4]芳烃底部空间定向的协同作用,而不是与四酚大环或单独的药效基团磺酰脒基团的作用。考虑到已确定的杯[4]芳烃C - 90对质膜Ca2 +,Mg2 + -ATP酶活性抑制作用的动力学模式,建立了未兴奋子宫肌细胞基础钙浓度控制的稳态动力学模型。据推测,所获得的结果可能为基于杯[4]芳烃C - 九零的新一代(“超分子”)药理制剂——子宫基础张力刺激剂的研发提供前景。