Selective inhibition of smooth muscle plasma membrane transport Ca2+,Mg2+-ATPase by calixarene C-90 and its activation by IPT-35 compound

摘要

We investigated the influence of calixarene C-90 and IPT-35 on plasma membrane Ca2+-pumping ATPase (PMCA), intracellular calcium homeostasis and myometrium smooth muscle strain contractions. It has been shown that both effectors (100 mu M) affect PMCA enzymatic activity: calixarene C-90 inhibits it by 75% and IPT-35 activates it by 40%. These compounds don't affect the Mg2+-ATPase, Mg2+-independent Ca2+-ATPase and Na+,K+-ATPase enzymatic activities. C-90 inhibition coefficient I-0.5 magnitude was approximately 20 pM and the Hill coefficient n(H) was 0.55. For IPT-35 activation, constant A(0.5) was 6.4 and n(H) was 0.7. Mathematical modeling demonstrated the implication of calixarene C-90 on unexcited myocytes, which allows for a precise change in cytoplasm Ca2+ concentration and an influence on basal muscle tonus. By the same method, we determined that IPT-35 has a little influence on Ca2+ concentration in unexcited myocytes. It was also shown that calixarene C-90 in vitro can increase velocity of oxytocin-initiated contractions, whereas IPT-35 can suppress this aforementioned parameter. These results are promising for the design of new pharmacological compounds as better regulators of uterine contractions. Calixarene C-90 can be used in obstetric cases for the simultaneous use of oxytocin for enhancing uterine contractions, and IPT-35 for its antispasmodic effect on uterine tone.