Effects of L-dopa and L-tyrosine on release of free and conjugated dopamine, homovanillic acid and dihydroxyphenylacetic acid from slices of rat striatum.

Conjugation (presumably with sulfate) is a demonstrable metabolic pathway for 3, 4-dihydroxyphenylethylamine (dopamine, DA) in brain. Studies were done to determine whether conjugation becomes of increased significance in the presence of precursors of DA. The effects of 3, 4-dihydroxyphenylalanine (L-DOPA) and L-tyrosine on the efflux of free and conjugated DA, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid from slices from striatum in rats were studied under quiescent conditions and during release evoked by 40 mM K+ or by 5 X 10(-5) M phenylethylamine (PEA). Conjugated DA was present in the basal efflux from striatal slices and the amounts present were increased during evoked release. More conjugated DA was present in superfusate during K+-evoked release than during PEA-evoked release. L-Tyrosine (5 X 10(-4) M or 5 X 10(-5) M) had little effect on the efflux of conjugated DA, but decreased the amounts of free DA released by PEA, and attenuated the increase in DOPAC that occurred during K+-evoked release of transmitter. L-DOPA (5 X 10(-5) M) increased the formation of conjugated DA, but to a lesser extent than that of free DA or of DOPAC. Thus even after the addition of precursors, conjugation remains a minor metabolic pathway for DA relative to O-methylation or oxidative deamination. The data also suggest that conjugation of DA occurs chiefly outside of the dopaminergic neurons in striatum.