Manganese and copper promote the binding of dopamine to "serotonin binding proteins" in bovine frontal cortex.
The authors previously reported that Fe2+ is capable of increasing the binding of dopamine and of serotonin to "serotonin binding proteins" which are present in soluble extracts from calf brain. In this study, it is shown that Mn2+ and Cu2+ are also capable of increasing the binding, but for dopamine only. As for Fe2+, Mn2+ and Cu2+ are likely to promote the binding by virtue of their ability to enhance the oxidation of dopamine into dopamine-O-quinone, a derivative which is known to undergo covalent association with sulfhydryl groups of proteins. Data such as the irreversible nature of the majority of the binding, the inhibitory action of reducing agents (sodium ascorbate) and of reagents which contain, or modify sulfhydryl groups (reduced glutathione) are compatible with such a mechanism. The three metal ions are also capable of inactivating part of the binding sites on SBP directly; this effect is more pronounced for Cu2+ than for Fe2+ and it is only weak for Mn2+. The Fe(2+)-mediated binding of dopamine is inhibited by the superoxide dismutase enzyme, and it was therefore suggested that Fe2+ enhances the oxidation of dopamine by virtue of its ability to produce superoxide radicals out of dissolved molecular oxygen. Such a mechanism does not appear to take place in the case of Mn2+ and Cu2+. Instead, it is likely that Cu2+ and dopamine form a complex which is highly susceptible towards oxidation by dissolved molecular oxygen. Mn2+, on the other hand, can easily be oxidized into Mn3+, which is capable to oxidize dopamine by itself.(ABSTRACT TRUNCATED AT 250 WORDS)
Velez-Pardo
C
C
Department of Protein Chemistry, Free University Brussels, St Genesius-Rode, Belgium.
Jimenez del Rio
M
M
Ebinger
G
G
Vauquelin
G
G
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D016166:Free Radical Scavengers; D005625:Frontal Lobe / Q000378:metabolism*; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011485:Protein Binding; D012701:Serotonin / Q000378:metabolism*; D013268:Stimulation, Chemical; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology
D002352:Carrier Proteins; D002614:Chelating Agents; D016166:Free Radical Scavengers; D013438:Sulfhydryl Compounds; C025366:serotonin-binding protein; D012701:Serotonin; D008345:Manganese; D003300:Copper; D007501:Iron; D013482:Superoxide Dismutase; D004298:Dopamine