Striatal L‐DOPA Decarboxylase Activity in Parkinson's Disease In Vivo: Implications for the Regulation of Dopamine Synthesis

Abstract

L-DOPA is a large neutral amino acid subject to transport out of, as well as into, brain tissue. Competition between dopamine synthesis and L-DOPA egress from striatum must favor L-DOPA egress if decarboxylation declines relatively more than transport in Parkinson's disease. To test this hypothesis, we injected patients with Parkinson's disease with a radiolabeled analogue of L-DOPA and recorded regional brain radioactivity as a function of time by means of positron emission tomography. We simultaneously estimated the activity of the decarboxylating enzyme and the amino acid transport. In the striatum of patients, we found the L-DOPA decarboxylase activity to be reduced in the head of the caudate nucleus and the putamen. However, the rate of egress of the DOPA analogue was unaffected by the disease and thus inhibited dopamine synthesis more than predicted in the absence of L-DOPA egress.

Enhanced [3H]DOPA and [3H]Dopamine Turnover in Striatum and Frontal Cortex In Vivo Linked to Glutamate Receptor Antagonism

“…It supports the speculation that the rate constant of DDC is regulated to optimize or adjust dopamine synthesis in living brain (Buckland et al, 1992;Zhu et al, 1992;Gjedde et al, 1993;Cumming et al, 1995).…”

Subchronic Haloperidol Downregulates Dopamine Synthesis Capacity in the Brain of Schizophrenic Patients In Vivo

“…However, in the living brain the DDC activity influences the fraction of substrate, which is directed to catecholamine synthesis rather than being exported from the brain. The presence of alternate fates for L-DOPA in vivo requires that regulation of DDC must also influence the rate of DA synthesis Gjedde et al, 1993). In support of this claim, the DDC activity in the striatum of living rats was potentiated by acute neuroleptic treatment and decreased by the DA presynaptic autoreceptor agonist apomorphine (Cumming et al, 1997).…”

Trace Amines and Their Receptors

“…Regulation of AADC by serotonergic receptors (Neff et al, 2006) and Nmethyl-D-aspartate (NMDA) glutamatergic receptors (Hadjiconstantinou et al, 1995;Fisher et al, 1998) has also been reported. There is also some evidence for AADC regulation associated with systemic lupus erythematosus (Bengtsson et al, 2016), Parkinson' disease (Gjedde et al, 1993), and schizophrenia (Reith et al, 1994). In experimental animals, regulation of AADC after spinal cord injury has also been reported Wienecke et al, 2014;Azam et al, 2015).…”