%0 Journal Article %A RICHARD HEIKKILA %A GERALD COHEN %T Further Studies on the Generation of Hydrogen Peroxide by 6-Hydroxydopamine %B Potentiation by Ascorbic Acid %D 1972 %J Molecular Pharmacology %P 241-248 %V 8 %N 2 %X We studied the inhibitory action of various compounds, including hydrogen peroxide, on the uptake of [3H]dopamine by rat brain slices. Dialuric acid, 6-hydroxydopamine, and 5-hydroxydopamine consumed oxygen and generated hydrogen peroxide in solution as a result of aerobic oxidation, as measured with an oxygen electrode. The regeneration by catalase of half the oxygen consumed by 6-hydroxydopamine confirmed that oxygen consumption was equal to H202 production. The rate of oxygen uptake (H202 production by dialuric acid or 6-hydroxydopamine was augmented by the addition of ascorbic acid. In addition, alloxan, which is the oxidized form of dialuric acid, consumed oxygen when ascorbate was added. The mechanism for this can be envisaged as reduction of the oxidized compounds by ascorbate, followed by reoxidation to form more H202, with continuous recycling. Concomitant with increased production of H202, there was increased inhibition of [3H]dopamine uptake. Ascorbate by itself did not inhibit the uptake of [3H]dopamine and did not produce measurable quantities of H202. 6-Hydroxydopamine, a compound that causes nerve terminal degeneration in vivo, was compared with 5-hydroxydopamine, which does not. As both compounds are structural analogues of dopamine, they can inhibit the uptake of [3H]dopamine into brain slices by competing for the uptake mechanisms. Additionally, both may inhibit uptake irreversibly by generating H2O2, which causes oxidative damage. 6-Hydroxydopamine produced H202 at about 12 times the rate yielded by 5-hydroxydopamine. Ascorbate potentiated H2O2 production by 6-hydroxydopamine but suppressed that from 5-hydroxydopamine. These findings are consistent with an important role for H2O2 in the 6-hydroxydopamine-induced degeneration of nerve terminals and may explain why 5-hydroxydopamine does not produce degenerative changes. ACKNOWLEDGMENT We thank Felicitas Cabbat for her expert technical assistance. %U https://molpharm.aspetjournals.org/content/molpharm/8/2/241.full.pdf