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

2009
Authors
Oreščanin-Dušić, Zorana
Milovanović, Slobodan
Blagojević, Duško
Nikolić-Kokić, Aleksandra

Radojicic, Ratko
Spasojević, Ivan

Spasić, Mihajlo

Article (Published version)
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Show full item recordAbstract
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 / diethyldithiocarbamateSource:
Redox Report, 2009, 14, 2, 48-54Publisher:
- 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
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Institution/Community
Institut za multidisciplinarna istraživanjaTY - 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 . .