Regulation of dopa biosynthesis by presynaptic dopamine receptors and ∝₂- adrenoreceptors

Abstract

The biosynthesis of the adrenergic neurotransmitters in the CNS is controlled by multiple regulatory systems. In addition to the feedback inhibition and possible allosteric changes of tyrosine hydroxylase, it became apparent that the biosynthesis of dopamine (DA) is controlled by the activity state of the receptors in the synaptic cleft (Carlsson et al., 1972). We have shown that the inhibition of tyrosine hydroxylase by apomorphine in striatal slices and in synaptosomal preparations is due to a double action of this drug; one related to the inhibitory property of the catechol moiety, and the other related to the activation of the presynaptic receptors (Ebstein et al., 1974; Goldstein et al., 1976). The regulation of DOPA biosynthesis by presynaptic DA receptors was studied in vivo following inhibition of impulse flow in dopaminergic neurons by placement of lesions in the nigro-striatal pathway (Kehr et al., 1972), or following administration of gammabutyrolactone (GBL) (Walters and Roth, 1972). Recently, a number of studies have investigated the interactions of DA agonists with postsynaptic DA receptors by measuring in vitro their binding affinities to striatal membrane sites.