INFLUENCE OF GLUTATHIONE ON THE OXIDATION CHEMISTRY OF THE CATECHOLAMINERGIC NEUROTRANSMITTER DOPAMINE

In this study it is demonstrated that dopamine-o-quinone (DA-o-quinone ), generated by the electrochemically driven oxidation of the catechol aminergic neurotransmitter dopamine (DA) at physicological pH, is rapi dly scavenged by glutathione (GSH) to give, initially, 5-S-glutathiony ldopamine (5-S-Glu-DA). The latter conjugate is more easily oxidized t han DA to an o-quinone that reacts further with free GSH to give 2,5-b i-S-glutathionyldopamine (6), an even more easily oxidized compound. T he proximate oxidation product of 6, o-quinone (7), is the precursor o f 2,5,6-tri-S-glutathionyldopamine (8) and 4,7-bis-S-glutathionyl-5,6, dihydroxyindole (16). A p-quinone methide tautomer of o-quinone 7 is t he precursor of glutathionyl conjugates of DA which contain a glutathi onyl residue substituted in the ethylamino side-chain of the neurotran smitter. In the presence of equimolar or greater concentrations of GSH the normal oxidation pathway of DA to insoluble black indolic melanin polymer is blocked. The potential relevance of the in-vitro oxidation of DA in the presence of free GSH to an understanding of the degenera tion of nigrostriatal dopaminergic neurons in idiopathic Parkinson's d isease is discussed.