Mehanizmi relaksantnog efekta natrijum-sulfida na uterus pacova in vitro: efektorne vrste i ciljne molekulske strukture
Mechanisms of sodium sulphide relaxatory effect in rat uterus in vitro: reactive species and molecular targets
Doctoral thesis (Published version)
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Uterine contractions are important in many reproductive functions.Improper or irregular uterine activity may underlie the common pathologicaldisorders such as infertility, improper implantation, dysmenorrhea, weak uterinecontraction during labor and preterm labor. The contractile activity of the uterus isregulated by the complex electrophysiologic network which is highly sensitive tovarious pharmacological and signaling molecules. Remarkably, uterus is able toswitch from quiescence to oscillatory cycles of strong contractions. This isdependent on the activity of the cells being able to remodel their signallingsystems.Endogenously produced hydrogen sulphide (H2S), which, together withNO and CO, is a recognized gasotransmitter, also appears to be a signallingmolecule in rat uterus. Hydrogen sulphide reduces uterine contractility, and it isrecognized as a promising treatment for uterine disorders. There were no studiesabout mechanistic insights of its relaxatory effect, done so far, and thus is ofpotential interest. It is not currently known whether the biological effects of H2Sare mediated directly by H2S or by its derivatives, the most important being thethiolate anion HS−. The results presented in this thesis imply that it appearsunlikely that molecular and anionic forms have pharmacologically identicalactions, including the regulation of contractility. Pharmacological effects ofH2S/HS− were compared to effects of methanethiol (CH3SH, mimicks H2S), andobserved differences might be a consequence of the specific actions of HS−. Thiscomparison may represent a useful tool for discrimination between differentactions of H2S and HS−. The metabolism of CH3SH is intertwined with hydrogensulfide (H2S), since the later is methylated to CH3SH and this methylation may be anew way of modulation of H2S effects in vivo.We investigated the involvement of ion channels (K+, Ca2+, Cl−) in therelaxation of rat uteri induced by H2S/HS−. We found that sulphide induces...
Keywords:Uterus; Contractility; H2S/ HS−; CaCC; Bestrophin; ROS
Source:University of Belgrade, Faculty of Chemistry, 2015, 1-161