Interaction of serotonin- and dopamine-related neurotoxins with "serotonin binding proteins" in bovine frontal cortex.
Binding of [3H]serotonin and [3H]dopamine to serotonin-binding proteins (SBP) from soluble extracts of bovine frontal cortex is increased by Fe2+. This group recently attributed this effect of Fe2+ to its ability to enhance the oxidation of [3H]serotonin and [3H]dopamine in the presence of dissolved molecular oxygen, and to the ability of the formed oxidation products to bind covalently to cysteine residues of SBP. In this study it is shown that the binding of both ligands is potently inhibited by dopamine as well as by several catecholamine-and serotonin-related neurotoxins: adrenochrome, 5,6-dihydroxytryptamine, 5,7-dihydroxytryptamine, 6-hydroxydopamine and 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline. In contrast, serotonin can only potently inhibit part (36%) of the [3H]dopamine binding, while 1,2,3,4-tetrahydroisoquinoline is only a weak competitor for both ligands. Potent inhibition by the toxins is associated with the presence of electrophilic centres at the aromatic ring, either of the products themselves (adrenochrome) or of their oxidation products (all other competitors). These findings suggest that "SBP" represent an important target for the Fe(2+)-mediated binding of [3H]-serotonin, [3H]dopamine and related neurotoxins.
Jimenez del Rio
M
M
Department of Protein Chemistry, Free University Brussels, St Genesius-Rode, Belgium.
Velez Pardo
C
C
Pinxteren
J
J
De Potter
W
W
Ebinger
G
G
Vauquelin
G
G
D000323:Adrenochrome / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005296:Ferrous Compounds; D007546:Isoquinolines / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism* / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
D002352:Carrier Proteins; D018492:Dopamine Antagonists; D005296:Ferrous Compounds; D007546:Isoquinolines; D009498:Neurotoxins; D012702:Serotonin Antagonists; C025366:serotonin-binding protein; D012701:Serotonin; C020748:ferrous sulfate; C003876:6,7-dihydroxytetrahydroisoquinoline; D000323:Adrenochrome; D016627:Oxidopamine; D004298:Dopamine