Diethyldithiocarbamate potentiates the effects of protamine sulphate in the isolated rat uterus.
Journal Article
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-DDC(2) 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-DDC(2) 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.
Full Text
Duke Authors
Cited Authors
- Orescanin-Dusić, Z; Milovanović, S; Blagojević, D; Nikolić-Kokić, A; Radojicić, R; Spasojević, I; Spasić, M
Published Date
- January 2009
Published In
Volume / Issue
- 14 / 2
Start / End Page
- 48 - 54
PubMed ID
- 19389271
Pubmed Central ID
- 19389271
Electronic International Standard Serial Number (EISSN)
- 1743-2928
International Standard Serial Number (ISSN)
- 1351-0002
Digital Object Identifier (DOI)
- 10.1179/135100009x392476
Language
- eng