Effects of L-dopa on accumulation and efflux of monoamines in particles of rat brain homogenates.

l-Dopa enhanced release of exogenous labeled norepinephrine, dopamine and serotonin from particles in homogenates of rat brain. The addition of an aromatic l-amino acid decarboxylase inhibitor, DL-α-methyldopahydrazine (MK-485), in a concentration which greatly decreased the conversion of dopa to dopamine, markedly reduced the l-dopainduced release of monoamines. MK-485 itself did not influence the spontaneous release of monoamines nor affect the accumulation of l-dopa. Furthermore, dopamine was much more effective than l-dopa in evoking amine release. These observations suggest that the release of monoamines by l-dopa is mediated by dopamine. After intracisternal administration of 6-hydroxydopamine in doses sufficient to decrease endogenous catecholamine content by two-thirds or more, less catecholamines (dopamine or norepinephrine) were accumulated by brain particles and less were released by l-dopa. Serotonin content of brain was unaltered by 6-hydroxydopamine and the accumulation of serotonin as well as its release by l-dopa remained relatively unaffected. These results suggest that serotonin is released by dopamine derived from decarboxylation of dopa in serotonergic neurons. Accumulation of tyrosine, dopa and 5-hydroxytryptophan were slightly reduced by pretreatment with 6-hydroxydopamine, whereas accumulation of γ-aminobutyric acid was essentially unaffected.