Прегледај по Аутор "Spasić, Mihajlo"

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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.