DOPAMINE SYNTHESIS IN RAT-BRAIN STRIATAL SYNAPTOSOMES .2. DIBUTYRYL CYCLIC ADENOSINE 3'=5'-MONOPHOSPHORIC ACID AND 6-METHYLTETRAHYDROPTERINE-INDUCED SYNTHESIS INCREASES WITHOUT AN INCREASE IN ENDOGENOUS DOPAMINE RELEASE

Abstract

The effects of N6,O2''-dibutyryl cyclic(c)AMP [dibutyryl cAMP] DL-6-methyl-5,6,7,8-tetrahydropterine (6-MPH4) and tyramine on dopamine synthesis and endogenous dopamine release in rat brain striatal synaptosomes were examined. Dibutyryl cAMP (1 mM) produced a 100% increase in dopamine synthesis but had no effect on endogenous dopamine release. Veratridine (75 .mu.M) did not further stimulate dibutyryl cAMP-treated tissue. 6-MPH4 (0.1 mM) stimulated synthesis without stimulating dopamine release. The stimulation produced by 6-MPH4 was additive to the stimulations produced by either dibutyryl cAMP or veratridine. Tyramine (10-4 M) inhibited synthesis, while increasing dopamine release. These data suggest that dopamine-releasing agents may have differential effects upon dopamine synthesis, depending on their mechanism of release, dopamine synthesis can be stimulated independently of endogenous dopamine release and the pteridine cofactor necessary for tyrosine hydroxylation is not normally present at saturating levels.