Вплив каліксарену С-90 на скоротливу активність гладеньких м’язів міометрія щурів

Abstract

It is known that calix[4]arene with cipher C-90 selectively and with high affinity inhibits Ca 2+ ,Mg 2+ -ATPase of smooth muscle cells plasma membrane preparations. The work wis devoted to investigation of the influence of calixarene C-90 (10 µM) on spontaneous and induced (high-potassium solution and oxytocin) contractions of rat uterus longitudinal smooth muscles. Contractile activity was studied tensometrically in the isometric mode, analysis of the kinetic properties of contractions was performed by the calculation of the normalized maximal velocity of contraction ( V n с ) and relaxation ( V nr ) phases. Calixarene C-90 changed the spontaneous contractile activity, causing a decrease in amplitude and has no significant effect on the frequency, while slowing down of the relaxation phase of individual contractions (decreasing parameter V nr ) occurred. In the presence of non-selective NO-synthase inhibitor L-NAME (100 µM), calixarene C-90 did not cause a reduction of the amplitude of spontaneous contractions and the speed of relaxation phase returned to the control level. Furthermore, calixarene C-90 was equally contributing factor to reduced force of both oxytocin-induced (0.1 IU) and K + -induced (80 mM) contractions without affecting the nature of the increase in contractile force responses (normalized maximal velocity of contraction phase stayed at control level). The relaxation velocity of caused contractions recieved opposite changes depending on the nature of the contractile stimulation: in case of oxytocin-evoked contractions – decreased, while for K + -induced contractions – increased. In the presence of L-NAME calixarene C-90 did not cause inhibition of the maximal force K + - and oxytocin-induced contractions, but evoked changes in the kinetical para­meters of contractile responses (decrease V nr ). Thus, blocking of NO synthesis resulted in the removal of inhibiting both spontaneous and evoked contractions of smooth muscle myometrium under the influence of calixarene C-90. These results suggest that inhibition force of uterus smooth muscle contractions under the influence of calixarene C-90 is by NO-dependent way, whereas slow relaxation (decrease in normalized maximal velocity V nr ) is caused by the inhibition of Ca 2+ -transport function of the plasma membrane calcium pump. Keywords : smooth muscle, uterus, contraction, kinetical parameters, calixarene C-90, plasma membrane calcium pump, nitric oxide.