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Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus

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2009
332.pdf (977.2Kb)
Authors
Oreščanin-Dušić, Zorana
Milovanović, Slobodan
Blagojević, Duško
Nikolić-Kokić, Aleksandra
Radojicic, Ratko
Spasojević, Ivan
Spasić, Mihajlo
Article (Published version)
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Abstract
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 Cui 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 Cui 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 hydroxy radical generating Fenton reaction, DDC can also prevent iron-related pathophysiological manifestations. Such permissive roles of DDC open the possibi...lity for application of its pharmacological form (disulfiram) to a wider spectrum of pathophysiological conditions related to smooth muscles.

Keywords:
uterus / protamine sulphate / nitric oxide / diethyldithiocarbamate
Source:
Redox Report, 2009, 14, 2, 48-54
Publisher:
  • Taylor & Francis Ltd, Abingdon
Funding / projects:
  • The Role of Redox-Active Substances in the Maintenance of Homeostasis (RS-143034)
  • Biofizička istraživanja membranskih procesa: interakcija membranskih receptora i kanala sa spoljašnjim faktorima i intracelularna regulacija (RS-143016)

DOI: 10.1179/135100009X392476

ISSN: 1351-0002

PubMed: 19389271

WoS: 000265636800001

Scopus: 2-s2.0-69249116672
[ Google Scholar ]
7
6
URI
http://rimsi.imsi.bg.ac.rs/handle/123456789/335
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Institut za multidisciplinarna istraživanja
TY  - JOUR
AU  - Oreščanin-Dušić, Zorana
AU  - Milovanović, Slobodan
AU  - Blagojević, Duško
AU  - Nikolić-Kokić, Aleksandra
AU  - Radojicic, Ratko
AU  - Spasojević, Ivan
AU  - Spasić, Mihajlo
PY  - 2009
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/335
AB  - 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 Cui 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 Cui 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 hydroxy 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.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Redox Report
T1  - Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus
EP  - 54
IS  - 2
SP  - 48
VL  - 14
DO  - 10.1179/135100009X392476
ER  - 
@article{
author = "Oreščanin-Dušić, Zorana and Milovanović, Slobodan and Blagojević, Duško and Nikolić-Kokić, Aleksandra and Radojicic, Ratko and Spasojević, Ivan and Spasić, Mihajlo",
year = "2009",
abstract = "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 Cui 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 Cui 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 hydroxy 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.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Redox Report",
title = "Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus",
pages = "54-48",
number = "2",
volume = "14",
doi = "10.1179/135100009X392476"
}
Oreščanin-Dušić, Z., Milovanović, S., Blagojević, D., Nikolić-Kokić, A., Radojicic, R., Spasojević, I.,& Spasić, M.. (2009). Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus. in Redox Report
Taylor & Francis Ltd, Abingdon., 14(2), 48-54.
https://doi.org/10.1179/135100009X392476
Oreščanin-Dušić Z, Milovanović S, Blagojević D, Nikolić-Kokić A, Radojicic R, Spasojević I, Spasić M. Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus. in Redox Report. 2009;14(2):48-54.
doi:10.1179/135100009X392476 .
Oreščanin-Dušić, Zorana, Milovanović, Slobodan, Blagojević, Duško, Nikolić-Kokić, Aleksandra, Radojicic, Ratko, Spasojević, Ivan, Spasić, Mihajlo, "Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus" in Redox Report, 14, no. 2 (2009):48-54,
https://doi.org/10.1179/135100009X392476 . .

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