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

Published

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