Прегледај по Аутор "Milovanović, Slobodan"

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    Diethyldithiocarbamate 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, Mihajlo
    Protamine 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.
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    Effects 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, Duško
    Protamine 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.
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    Essential Oil of Satureja montana L. from Herzegovina: Assessment of Composition, Antispasmodic, and Antidiarrheal Effects
    (ACG Publications, 2023) Kulić, Milan; Drakul, Dragana; Sokolović, Dragana; Kordić-Bojinović, Jelena; Milovanović, Slobodan; Blagojević, Duško
    Satureja montana L. (SM) has a long traditional use as a spice and a medicine for various gastrointestinal disorders, including painful spasms and diarrhea. Contrary to conventional drugs, administration of SM and its extracts are considered safe. Previous studies have shown that the essential oils (EOs) of SM from different areas are rich in monoterpenes, sesquiterpenes, diterpens, and phenolic compounds, including flavonoids, tannins, and acids with great composition variability. Determination of composition of EO from Herzegovinian SM done by gas chromatographyflame ionization detection and gas chromatography mass spectrometry (GC-FID and GC/MS, respectively) revealed carvacrol as a primary substance followed by γ-terpinene, p-cymene, and β-caryophyllene. Ex vivo spasmolitic activity caused by EO was evident in different types of isolated rat ileum function with the most potent effect on spontaneous activity followed by electrical field stimulation and KCl- and CaCl2-induced activity. SMEO produced in vivo antidiarreal activity on castor oil-induced diarrhea in young rats and showed the potential to cause a decrese water content in the feces of adult Wistar rats.This study indicates that effects of SM on the intestinum could be mediated through combination of Kv channel activation and Ca channel blockade, but additional mechanisms might be involved. The results of this study corroborate the traditional use of SM as antispasmodic, antidiarrheal, and antisecretory agents.
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    The 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, Duško
    MgSO4 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.