Selective inhibition of smooth muscle plasma membrane transport Са2+,Mg2+-АТРase by calixarene C-90 and its activation by IPT-35 compound

Gen Physiol Biophys. 2018 Mar;37(2):223-231. doi: 10.4149/gpb_2017035.


We investigated the influence of calixarene C-90 and IPT-35 on plasma membrane Ca2+- pumping АТРase (PMCA), intracellular calcium homeostasis and myometrium smooth muscle strain contractions. It has been shown that both effectors (100 μM) 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+-АТРase, Mg2+-independent Са2+-АТРase and Na+,K+-АТРase enzymatic activities. C-90 inhibition coefficient I0.5 magnitude was approximately 20 μM and the Hill coefficient nH was 0.55. For IPT-35 activation, constant А0.5 was 6.4 and nH 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.

MeSH terms

  • Animals
  • Calixarenes / pharmacology*
  • Cell Membrane / metabolism
  • Female
  • Muscle, Smooth / drug effects*
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Rats
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
  • Uterine Contraction / drug effects*
  • Uterus / drug effects


  • Calixarenes
  • Sodium-Potassium-Exchanging ATPase