Прегледај по Аутор "Milovanović, Slobodan"
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- СтавкаDiethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus(Taylor & Francis, 2009) Oreščanin-Dusić, Zorana; Milovanović, Slobodan; Blagojević, Duško; Nikolić-Kokić, Aleksandra; Radojičić, Ratko; Spasojević, Ivan; Spasić, MihajloProtamine sulphate causes potassium ion channel-mediated relaxation of spontaneous and calcium ion-induced contractions of the isolated rat uterus. Diethyldithiocarbamate (DDC) potentiated the effect of protamine sulphate. A mechanism for DDC’s action was postulated on the basis of its interactions with divalent iron ions and Cu,Zn-SOD. DDC chelates divalent iron ions creating DDC-iron (Fe-DDC) complexes. Fe-DDC forms stable NO-Fe-DDC2 complexes by NO scavenging and de-nitrosylation processes, which in combination with DDC (5 mM) provoke inhibition of Cu,Zn-SOD resulting in specific oxidative conditions culminating in potassium ion channel opening, membrane hyperpolarisation, inhibition of calcium ion influx and subsequent muscle relaxation. As Fe-DDC and NO-Fe-DDC2 complexes exclude divalent iron ions from participating in the hydroxyl radical generating Fenton reaction, DDC can also prevent iron-related pathophysiological manifestations. Such permissive roles of DDC open the possibility for application of its pharmacological form (disulfiram) to a wider spectrum of pathophysiological conditions related to smooth muscles.
- СтавкаEffects of protamine sulphate on spontaneous and calcium-induced contractile activity in the rat uterus are potassium channels-mediated(Slovak Academy of Sciences, 2009) Oreščanin-Dušić, Zorana; Milovanović, Slobodan; Radojičić, Ratko; Nikolić-Kokić, Aleksandra; Appiah, Isabella; Slavić, Marija; Čutura, Neđo; Trbojević, Stevan; Spasić, Mihajlo; Blagojević, DuškoProtamine sulphate (PS) effect on spontaneous and calcium-induced rhythmic contractions of isolated virgin rat uteri was studied. PS caused dose-dependent relaxation of both types of contractions (two-way ANOVA, significant dose effects). Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 10–5 mol/l), methylene blue (MB; 0.9 × 10–6 mol/l) or propranolol (1.7 × 10–5 mol/l) enhanced PS-mediated uterine muscle relaxation of spontaneous contractions. Dosedependent relaxation of spontaneous active isolated rat uterus with PS was lower in uteri pretreated with single dose of tetraethylammonium (TEA; 6 × 10–3 mol/l), glibenclamide (2 × 10–6 mol/l) and 4-aminopyridine (4-AP; 10–3 mol/l). Calcium-induced activity of the isolated rat uterus pretreated with the same concentration of L-NAME, MB, or propranolol modified the kinetic of PS-induced relaxation without changes in EC50 values. Pre-treatment with glibenclamide, TEA and 4-AP significantly reduce PS relaxing effect of calcium-induced activity and according to EC50 values the order of magnitude was glibenclamide > TEA > 4-AP. PS is mixture of polyamines and may activate different signal-transduction pathways. Our results cleary demonstrate that in uterine smooth muscle PS act dominantly through potassium chanels and marginaly through β-adrenergic receptos or nitric oxide-dependent pathways.
- СтавкаThe role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus(Serbian Biological Society, 2019) Sokolović, Dragana; Drakul, Dragana; Oreščanin Dušić,; Tatalović, Nikola; Pecelj, Milica; Milovanović, Slobodan; Blagojević, DuškoMgSO4 is used as a tocolytic agent. It is considered to be a calcium channel antagonist, but a different mechanism of its action might be involved. The aim of this study was to examine the contribution of calcium concentrations and potassium channels in the mechanism of MgSO4-mediated uterine relaxation. Isolated uteri from female Wister rats were treated with increasing MgSO4 concentrations (0.1-30 mM). MgSO4 induced dose-dependent inhibition of spontaneous activity. Addition of Ca2+ (6 mM and 12 mM) stimulated uterine contractile activity and attenuated the inhibitory activity of MgSO4. In order to analyze the role of different subtypes of potassium channels, Ca2+-stimulated uteri were pretreated with glibenclamide (Glib), a selective ATP-sensitive potassium channel inhibitor (KATP), tetraethylammonium (TEA), a non-specific inhibitor of large conductance calcium-activated potassium channels (BKCa), and 4-aminopyridine (4-AP), a voltage-sensitive potassium channel inhibitor (Kv), at concentrations that had no effect per se. Pretreatment with 4-AP had no effect on MgSO4-mediated relaxation of Ca2+-stimulated uteri. The relaxing effect of MgSO4 was potentiated by pretreatment with glibenclamide. Pretreatment with TEA attenuated the MgSO4-mediated decrease in frequency. Our results suggest that MgSO4 acts as a general calcium antagonist that influences Ca2+-mediated potassium channels. Furthermore, it seems that MgSO4 uterine relaxation activity is partially mediated by selective ATP sensitive potassium channels, suggesting an ATP-dependent role.