INTERACTION OF SEROTONIN-RELATED AND DOPAMINE-RELATED NEUROTOXINS WITH SEROTONIN BINDING-PROTEINS IN BOVINE FRONTAL-CORTEX

Binding of [H-3]serotonin and [H-3]dopamine to serotonin-binding prote ins (SBP) from soluble extracts of bovine frontal cortex is increased by Fe2+. This group recently attributed this effect of Fe2+ to its abi lity to enhance the oxidation of [H-3]serotonin and [H-3]dopamine in t he presence of dissolved molecular oxygen, and to the ability of the f ormed oxidation products to bind covalently to cysteine residues of SB P. In this study it is shown that the binding of both ligands is poten tly inhibited by dopamine as well as by several catecholamine- and ser otonin-related neurotoxins: adrenochrome, 5,6-dihydroxytryptamine, 5,7 -dihydroxytryptamine, 6-hydroxydopamine and 6,7-dihydroxy-1,2,3,4-tetr ahydroisoquinoline. In contrast, serotonin can only potently inhibit p art (36%) of the [H-3]dopamine binding, while 1,2,3,4-tetrahydroisoqui noline is only a weak competitor for both ligands. Potent inhibition b y 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 finding s suggest that ''SBP'' represent an important target for the Fe2+-medi ated binding of [H-3]serotonin, [H-3]dopamine and related neurotoxins.