Inhibition of Dopa-production in Striatal Synaptosomes by the R(−) and the S(+) Enantiomers of Apomorphine

The mechanism of the regulation of dopamine (DA) biosynthesis in dopaminergic nerve terminals is still controversial. Most authors agree that extraneuronal DA or other dopaminergic drugs influence tyrosine hydroxylase (TH) via presynaptic autoreceptors. The dopamine agonist R(−)-apomorphine retains its efficiency in blocking DOPA-production in striatal slices or synaptosomes, reinforcing the concept of an autoreceptor-mediated regulation of DOPA-production. However, the antagonism of neuroleptics on the R(−)apomorphine-induced inhibition of DOPA-production in vitro is not very marked. Therefore, Goldstein et al. (1976) suggested that part of the R(−)-apomorphine effect is related to the inhibitory property of its catechol moiety. Apomorphine exists both in R(−)- and S(+)-enantiomeric forms, the catechol moiety being unchanged. While R(−)-apomorphine possesses DA-agonistic activity, S(+)-apomorphine is considered to be a DA-antagonist (Goldman and Kebabian, 1984). Comparison of the effects of both enantiomers on soluble TH-activity and DOPA-production in striatal synaptosomes should, therefore, allow to discriminate an autoreceptor mediated effect on TH from a direct one.