Aromatic L-amino Acid Decarboxylase Activity Research Articles

Analysis of the Alternative Promoters that Regulate Tissue‐Specific Expression of Human Aromatic l‐Amino Acid Decarboxylase

Previously we identified two alternative first exons (exon N1 and exon L1) coding for 5' untranslated regions of human aromatic L-amino acid decarboxylase (AADC) and found that their alternative usage produced two types of mRNAs in a tissue-specific manner. To determine the cis-acting element regulating the tissue-specific expression of human AADC, we produced three kinds of transgenic mice harboring 5' flanking regions of the human AADC gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The transgene termed ACA contained -7.0 kb to -30 bp in exon N1, including the entire exon L1; ACN contained -3.6 kb to -30 bp in exon N1; and ACL contained -2.8 kb to -42 bp in exon L1. The ACA transgenic mice expressed CAT at extremely high levels in peripheral nonneuronal tissues, such as pancreas, liver, kidney, small intestine, and colon, that contained endogenous high AADC activity, whereas CAT immunoreactivity was not detected in either catecholaminergic or serotonergic neurons in the CNS. Thus, it was suggested that the ACA transgene contained the major part of cis-regulatory elements for the expression of AADC in peripheral nonneuronal tissues. On the other hand, the ACN transgenic mice moderately expressed CAT in various tissues except for the lung and liver, and the ACL transgenic mice showed moderate CAT expression only in the kidney.

The ultravist and melitrast influences on renal function in normal and pathological animals

In the presence of benserazide (50 μM), l-3,4-dihydroxyphenylalanine (l-DOPA) was rapidly accumulated in both LLC-PK1 and OK cells; equilibrium was attained at 30 min of incubation. For these LLC-PK1 and OK cells, the analysis revealed a rate constant of inward transport (kin in pmol/mg protein/min) of 3.6 ± 0.4 and 18.1 ± 0.3 and a rate constant of outward transport (kout in pmol/mg protein/min) of 1.0 ± 0.1 and 5.2 ± 0.1, respectively. Nonlinear analysis of the saturation curves for LLC-PK1 and OK cells revealed a Km (in μM) of 86 ± 12 and 14 ± 4, respectively. The cellular accumulation of the substrate was temperature-dependent and stereoselective. Aromatic l-amino acid decarboxylase (AAAD) activity was determined in cell homogenates; nonlinear analysis of the saturation curves revealed, for LLC-PK1 and OK cells, a Km (in μM) of 1866 ± 107 and 845 ± 153 and a Vmax (in nmol/mg protein/15 min) of 4.4 ± 0.1 and 0.9 ± 0.1, respectively. In the absence of benserazide, only a limited amount of the l-DOPA taken up was decarboxylated to dopamine in cell monolayers; the Km value (in μM) for decarboxylation of intracellular l-DOPA in LLC-PK1 and OK cells was 61 ± 14 and 108 ± 36, respectively. A low amount of newly formed dopamine was found to escape to the apical bathing fluid. This outward transfer of newly formed dopamine was a nonsaturable process up to 300 μM intracellular dopamine. In conclusion, the data presented here show that OK cells are endowed with a more efficient l-DOPA uptake system than LLC-PK1 cells, but the latter are endowed with a significantly higher AAAD activity than OK cells. In both cell lines, intracellular l-DOPA is rapidly converted to dopamine, some of which diffuses out of the cell.

Altered Basal Release and Pressor Effect of L-DOPA in the Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats

1. Transmitter-like L-DOPA functions as a tonic to produce postsynaptic cardiopressor responses in the rostral ventrolateral medulla (RVLM) of rats. We attempted to clarify whether a transmitter-like L-DOPA system is altered in the RVLM of spontaneously hypertensive rats (SHR) to maintain the hypertension. 2. By microdialysis of left RVLM area, the basal L-DOPA release was higher in SHR than in Wistar-Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 mu mol/L) to a similar degree in both strains. TTX-sensitive L-DOPA release was higher in SHR than in WKY. 3. L-DOPA (10-600 ng) and L-glutamate (10-300 ng) microinjected into left RVLM produced dose-dependent hypertension and tachycardia. Pressor but not tachycardiac responses to L-DOPA at lower doses were slightly greater in SHR than in WKY, whereas no difference to L-glutamate was observed in either strain. 4. In RVLM regions, there was no difference of tyrosine hydroxylase activity in SHR or WKY; however, L-aromatic amino acid decarboxylase activity was lower in SHR than in WKY. 5. Enhanced presynaptic neuronal L-DOPA release, including a decrease in decarboxylation and sensitization of postsynaptic pressor sites to L-DOPA in RVLM, may be involved in the maintenance of hypertension in SHR.

Distribution of Aromatic L-amino Acid Decarboxylase Activity in Tissues of Skipjack

Distribution of Aromatic L-amino Acid Decarboxylase Activity in Tissues of Skipjack

Effects of gliosis on dopamine metabolism in rat striatum

Neuroimplantation is inevitably accompanied by gliosis. Although graft-induced trophic effects on host neurons may be mediated by glial cells, the effects of gliosis on dopamine (DA) metabolism remains unclear. To examine these effects, basic fibroblast growth factor (bFGF) was directly infused into the striatum of 12 male rats (250–280 g). One week later, substantial gliosis was demonstrated in the infused striatum by immunochemical staining for glial fibrillary acidic protein (GFAP) and quantified by GFAP Western blot analysis. One week after bFGF infusion, extracellular DA and its metabolites were measured by in vivo microdialysis using HPLC. Infusion of l-DOPA through the dialysis probe resulted in a 60% reduction in the l-DOPA-induced DA peak in the gliotic striatum compared with the normal side. After l-DOPA infusion, dihydroxyphenylacetic acid (DOPAC) levels were similar between the gliotic and normal striatum. In contrast, homovanillic acid (HVA) levels were 26% higher in the gliotic striatum. Enzyme assays demonstrated that aromatic l-amino acid decarboxylase activity was unchanged in the gliotic striatum, but both MAO-A and MAO-B activities increased by 23% and 21%, respectively. These results suggest that the reduced striatal DA peak in the gliotic striatum after l-DOPA administration was due to accelerated DA catabolism through enhanced MAO activity. The bFGF-induced striatal gliosis may serve as a model to study neurotransmitter metabolism in the gliotic brain caused by disease processes, aging, or tissue grafting.

Phorbol Ester Administration Transiently Increases Aromatic l‐Amino Acid Decarboxylase Activity of the Mouse Striatum and Midbrain

Aromatic L-amino acid decarboxylase (AAAD) is required for the synthesis of catecholamines, serotonin, and the trace amines. We found that the protein kinase C activator phorbol 12-myristate 13-acetate administered intracerebroventricularly transiently increased AAAD activity by 30-50% over control values within approximately 30 min in the striatum and midbrain of the mouse. The enzyme increase was manifested as an apparent increase of Vmax with little change of Km for either L-3,4-dihydroxyphenylalanine or pyridoxal phosphate. Chelerythrine, a protein kinase C inhibitor, prevented the phorbol ester-induced increase of AAAD. Moreover, okadaic acid, a serine/threonine-selective protein phosphatase 1 and 2A inhibitor, also increased AAAD activity in the mouse striatum and midbrain. Taken together, these observations suggest that protein kinase C-mediated pathways modulate AAAD activity in vivo.

Regulation of aromatic l‐amino acid decarboxylase in rat striatal synaptosomes: effects of dopamine receptor agonists and antagonists

1. In this study we investigated the effects of dopamine receptor agonists and antagonists on rat striatal synaptosomal aromatic L-amino acid decarboxylase (AADC) activity. 2. The results show that 10(-5)-10(-7) M cis-flupenthixol increased the striatal synaptosomal AADC activity (by 25% to 57%) in a time-dependent manner. SCH 23390 and remoxipride alone had little or no effect on striatal synaptosomal AADC activity, but in combination they increased AADC activity by 20%, suggesting that the increases in striatal synaptosomal AADC activity occurred only after blockade of both dopamine D1 and D2 receptors. 3. Treatment with (+)-amphetamine and (+/-)-2-(N-phenylethyl-N-propyl)amino-5- hydroxytetralin hydrochloride ((+/-)-PPHT) produced a reduction of striatal synaptosomal AADC activity in a concentration- and time-dependent manner. SKF 38393 and (-)-quinpirole, however, exhibited no effect on striatal synaptosomal AADC activity, suggesting that only the mixed dopamine receptor agonists can reduce the AADC activity. Incubation with apomorphine at a concentration of 10(-4) M inhibited the AADC activity by 74% and this inhibition cannot be antagonized by SCH 23390, remoxipride or cis-flupenthixol, suggesting that apomorphine-induced inhibition of striatal synaptosomal AADC activity was not mediated by dopamine receptors. 4. cis-Flupenthixol can reverse the reduction of AADC activity induced by (+)-amphetamine and (+/-)-PPHT. The inhibition of AADC activity elicited by (+/-)-PPHT also can be reversed by SCH 23390 and remoxipride. 5. The inhibition of striatal synaptosomal AADC activity induced by (+/-)-PPHT is calcium-dependent and protein kinase C may play a role in the regulation of striatal AADC activity. 6. These studies show that striatal synaptosomal AADC activity is regulated by dopamine receptors and indicate that in vitro dopamine DI and D2 receptors have a synergistic effect in this regulation.

The effects of monoamine oxidase B inhibition on dopamine metabolism in rats with nigro-striatal lesions

The purpose of this study was to examine whether monoamine oxidase type B (MAO-B) has a role in striatal dopamine metabolism in animals with a unilateral lesion of the medial forebrain bundle, and whether 2-phenylethylamine (PE) could have a role in amplification of dopamine (DA) responses in DA depleted striatum. Inhibition of MAO-B did not alter DA metabolism in lesioned striata. PE accumulation decreased with loss of DA as long as there was no DA dysfunction. In lesioned striata with dysfunction of DA transmission at the synaptic level, PE accumulation increased, suggesting a compensatory increase in PE synthesis. This increase in PE levels does not appear to be mediated by an increase in the total striatal aromatic L-amino acid decarboxylase (AADC) activity. We conclude that inhibition of MAO-B has no effect on DA metabolism in the hemi-parkinsonian rat striatum and that PE could be involved in the antiparkinsonian action of MAO-B inhibitors.

Regulation of striatal aromatic L-amino acid decarboxylase: Effects of blockade or activation of dopamine receptors

Previous experiments have shown that blockade of dopamine D 1 or D 2 receptors by SCH 23390 or pimozide increases aromatic L-amino acid decarboxylase (AADC) activity in the rat striatum and the mesolimbic system. This study examined whether other dopamine receptor antagonists affect AADC activity and if there is an interaction between dopamine D 1 and D 2 receptor blockade on AADC activity. The possible effect of dopamine receptor agonists on AADC activity has been investigated as well. Administration of cis-flupenthixol (0.5 and 1 mg/kg) increased striatal AADC activity (by 25 and 26% above controls) and similar effects were observed with remoxipride (0.5–4 mg/kg) (by 18–27% above controls). Pretreatment with cycloheximide (10 mg/kg) did not change the increases produced by cis-flupenthixol (0.5 mg/kg). The administration of non-neuroleptic trans-flupenthixol did not change AADC activity. Combined treatment with SCH 23390 (0.1 mg/kg) and remoxipride (0.5 mg/kg), but not combination of SCH 23390 (0.1 mg/kg) and pimozide (0.3 mg/kg), showed higher increases of AADC activity than by the individual treatments, suggesting an interaction between the effects of the two drugs. Bromocriptine, but not (−)-quinpirole and d-amphetamine, significantly reduced the striatal AADC activity by 23% at the dose of 10 mg/kg. The results further demonstrate that AADC is a regulated enzyme in the rat brain.

GM1 ganglioside improves dopaminergic markers of rat mesencephalic cultures treated with MPP+

Rat embryonic mesencephalic cultures were employed to evaluate the consequences of adding GM1 ganglioside to cultures lesioned with the selective neurotoxin 1-methyl-4-phenylpyridinium (MPP+). MPP+ reduced dopamine and DOPAC content, dopamine uptake, aromatic L-amino acid decarboxylase activity, and the number of tyrosine hydroxylase-immunopositive neurons. The immunopositive neurons that remained were aberrant. All of these parameters were partially restored by adding GM1 ganglioside to the cultures. The response to GM1 was not altered by prior treatment of the cultures with cytosine beta-D-arabinofuranoside to reduce the number of glial cells. Dopamine uptake activity restored by GM1 was lost if GM1 was removed from the culture.

Dopamine formation, from its immediate precursor 3,4-dihydroxyphenylalanine, along the rat digestive tract.

The formation of dopamine, from L-3,4-dihydroxyphenylalanine (L-dopa), in fragments of non-glandular and glandular stomach, duodenum, jejunum, ileum and proximal and distal colon of the rat was examined. The deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (dopac) was also studied. The synthesis of dopamine in tissues incubated with 500 microM L-dopa for 20 min in conditions of catechol-O-methyltransferase (Comt) inhibition was found to be in the duodenum, jejunum and ileum 2-fold that in the proximal colon, 6-fold that in the glandular stomach and 120-fold that in the non-glandular stomach and distal colon. The formation of dopac in these tissues followed the pattern of amine formation. In the jejunum, the formation of dopamine and dopac was found to be dependent on the concentration of L-dopa (50 to 5000 microM) used. In another set of experiments, it was found that the formation of dopamine in jejunal segments loaded with increasing concentrations of L-dopa (50, 100 and 500 microM) was a time-dependent process. The rate constant (k) of formation of dopamine as a function of time was found to be similar (0.050 +/- 0.005) with either concentration of L-dopa; the rate constant of dopac formation in these experiments was, in contrast, found to be greater at the highest concentrations of L-dopa (100 and 500 microM). Aromatic L-amino acid decarboxylase (Aaad) activity determined in homogenates of the jejunal mucosa was found to be twice that observed in homogenates of the remaining jejunal wall (muscular).(ABSTRACT TRUNCATED AT 250 WORDS)

Aromatic L-amino acid decarboxylase activity of mouse striatum is modulated via dopamine receptors.

Aromatic L-amino acid decarboxylase (AAAD) activity is enhanced in the striatum of control and MPTP-treated mice after administration of a single dose of the dopamine receptor antagonists haloperidol, sulpiride, and SCH 23390. MPTP-treated mice appear more sensitive to the antagonists, i.e., respond earlier and to lower doses of antagonists than control mice. The rise of AAAD activity induced by the antagonists is prevented by pretreatment with cycloheximide. The apparent Km values for L-3,4-dihydroxyphenylalanine (L-DOPA) and pyridoxal 5-phosphate appear unchanged after treatment with the antagonists. Increased AAAD activity was observed also after subchronic administration of dopamine receptor antagonists or treatment with reserpine. A single dose of a selective dopamine receptor agonists had no effect on AAAD activity. In contrast, administration of L-DOPA, quinpirole, or SKF 23390 for 7 days lowers AAAD activity in the striatum. We conclude that AAAD is modulated in striatum via dopaminergic receptors.

Evidence for Cyclic AMP‐Mediated Increase of Aromatic L‐Amino Acid Decarboxylase Activity in the Striatum and Midbrain

Aromatic L-amino acid decarboxylase (AAAD) activity of mouse striatum and midbrain increased after an intracerebroventricular injection of either forskolin or 8-bromo-cyclic AMP. The increase was transient, peaking between 15 and 30 min and returning to baseline by approximately 90 min. The increase of AAAD activity after forskolin was not affected by pretreatment with cycloheximide. Kinetic studies indicated an apparent increase of Vmax with little change of the Km for L-DOPA or pyridoxal 5'-phosphate. We conclude that AAAD activity of striatum and midbrain can be modulated by a cyclic AMP-dependent process.

Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain.

The regional brain kinetics following 5-hydroxy-L-(beta-11 C)tryptophan and L-(beta-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or D-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 +/- 0.0007 (S. D) and 0.0121 +/- 0.0010 min-1 for 5-hydroxy-L-(beta-11 C)tryptophan and L-(beta-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(beta-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4 mg/kg of unlabelled compound. A decreased utilization rate of L-(beta-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.

Changes in activity and mRNA for rat tryptophan hydroxylase and aromatic l-amino acid decarboxylase of brain serotonergic cell bodies and terminals following neonatal 5,7-dihydroxytryptamine

In the present study, we examined time-dependent changes in activity, mRNA and immunoreactivity of the serotonin biosynthetic enzymes, tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC) in dorsal raphe nucleus (DRN), caudal brainstem and hypothalamus, following intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal rats. TPH activity in central serotonergic cell bodies and terminals was reduced to 20–30% of control levels at 1–8 weeks after neonatal, low-dose 5,7-DHT injection (24 μg free base). In contrast, AADC activity was either not changed or decreased to 40% of control levels, depending on the region. In situ hybridization and immunocytochemical staining indicated that 5,7-DHT caused a marked reduction in TPH and AADC message levels as well as the number of 5-HT and AADC-immunoreactive cells within the DRN as early as 1 week after 5,7-DHT. Even 15 weeks after drug administration recovery did not occur. This apparent neuronal loss was region-specific suggesting that some serotonergic neurons are more resistant to neonatal 5,7-DHT treatment than others. Taken together, these studies indicate that neonatal treatment with 5,7-DHT produces a marked and permanent (up to 15 weeks) reduction in the number of central serotonergic neurons.

Parallel Up‐Regulation of Catecholamine Biosynthetic Enzymes by Dexamethasone in PC12 Cells

We sought to investigate whether dexamethasone produces a coordinated, time-dependent effect on all enzymes in the catecholamine biosynthetic pathway in PC12 cells. The levels of mRNAs of tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), and dopamine beta-hydroxylase (DBH) were examined at 0, 6, 12, 24, and 48 h after dexamethasone (5 microM) treatment to PC12 cells. The levels of all enzyme mRNAs steadily increased for 24 h, although the increase of AADC mRNA content was slow. The increased mRNA levels of TH and AADC were maintained at 48 h, whereas the level of DBH mRNA was sharply decreased at 48 h. The maximally induced mRNA levels were approximately 5.0-, 2.4-, and 7.0-fold higher than the control levels of TH, AADC, and DBH, respectively. The elevation of enzyme activities was detected later than the increase in levels of mRNAs. The maximal activities of TH, AADC, and DBH were reached between 48 and 72 h with 3.6-, 1.8-, and 8.0-fold increases, respectively. Low, but detectable, phenylethanolamine N-methyltransferase (PNMT) activity was observed in PC12 cells, and dexamethasone increased its activity 5.6-fold at 72 h. The PNMT mRNA was easily detected by northern blot analysis after exposure for 24 h to dexamethasone. The data suggest that, in PC12 cells, dexamethasone up-regulates all catecholamine biosynthetic enzyme genes in a parallel fashion.

Identification of a neuron-specific promoter of human aromatic l-amino acid decarboxylase gene

We have cloned the 5′ region of human aromatic l-amino acid decarboxylase (AADC) gene in a cosmid and an overlapping lambda clone, and sequenced the first five exons. A 61 base pair (bp) non-coding, first exon containing for the 5′ end of a human pheochromocytoma AADC cDNA was localized 16 kb upstream of exon 2, in which translation is initiated. The transcription site was localized by RNAse mapping, primer extension and reverse transcription-PCR. The non-conventional cap site was preceded by a modified TATA box at position −29. A strong promoter was characterized in the 560 bp region upstream of the cap site by linkage to the reporter gene LacZ, and transfection in human neuroblastoma SK-N-BE and SK-N-BE-K2 cells. Using a series of constructs bearing a varying length of 5′ flanking region, three positive regulatory elements have been localized in the −560 to −394, −244 to −200 and −147 to −1 regions. Negative regulatory elements were localized in the −9000 to −560 and −394 to −316 regions. Surprisingly, constructs comprizing all or the major part of intron 1 were inactive, suggesting the presence of a silencer in the first intron, or uncorrect splicing events. The construct containing 560 bp of 5′ flanking sequence did not express in human cholinergic neuroepithelioma cells MC-I-XC, and in three non-neuronal cell lines which displayed high AADC activities: human pancreatic carcinoma cells AsPC-1, rat insulinoma cells RINm5F and mouse anterior pituitary cells AtT20. These data suggest that we have identified a neuron-specific AADC promoter. An extensive search for a second promoter responsible for AADC gene expression in non-neuronal cells only gave negative results.

Characterization of bovine aromatic l-amino acid decarboxylase expressed in a mouse cell line: comparison with native enzyme

Bovine aromatic l-amino acid decarboxylase (AADC) was expressed in a mouse cell line, using a bovine papilloma virus-derived expression vector containing the full coding region of bovine AADC. The recombinant bovine AADC was characterized biochemically and immunochemically and compared with the native bovine AADC. The specific activity of crude recombinant bovine AADC was 30-fold higher than that of crude native AADC. With regard to optimal pH, effects of pyridoxal phosphate concentration and K m for 3,4-dihydroxyphenylalanine as a substrate, both native and recombinant enzymes were essentially identical. Rabbit polyclonal antiserum directed against bovine adrenal AADC recognized on Western blot a single protein band (molecular mass = 55.000 Dalton) in both native and recombinant bovine AADC crude extracts. Furthermore, double immunodiffusion analysis showed a single precipitin line of confluence with both enzyme preparations, indicating immunological identity of native and recombinant bovine AADC. Northern blot analysis identified a single mRNA species (2.2 kb) from native and recombinant bovine AADC preparations. The recombinant bovine AADC has two charge isozymes corresponding to those of the native bovine enzyme, although their relative abundances are different between native and recombinant enzymes. Taken together, our results show that recombinant bovine AADC, expressed from bovine AADC cDNA in a mouse cell line is not only enzymatically active, but also shares many biochemical and immunochemical common features with native bovine AADC.

Aromatic L-amino acid decarboxylase activity of retina is modulated via aminergic receptors

Aromatic L-amino acid decarboxylase activity of retina is modulated via aminergic receptors

Regulation of Aromatic l‐Amino Acid Decarboxylase by Dopamine Receptors in the Rat Brain

Decarboxylation of phenylalanine by aromatic L-amino acid decarboxylase (AADC) is the rate-limiting step in the synthesis of 2-phenylethylamine (PE), a putative modulator of dopamine transmission. Because neuroleptics increase the rate of accumulation of striatal PE, these studies were performed to determine whether this effect may be mediated by a change in AADC activity. Administration of the D1 antagonist SCH 23390 at doses of 0.01-1 mg/kg significantly increased rat striatal AADC activity in an in vitro assay (by 16-33%). Pimozide, a D2-receptor antagonist, when given at doses of 0.01-3 mg/kg, also increased AADC activity in the rat striatum (by 25-41%). In addition, pimozide at doses of 0.3 and 1 mg/kg increased AADC activity in the nucleus accumbens (by 33% and 45%) and at doses of 0.1, 0.3, and 1 mg/kg increased AADC activity in the olfactory tubercles (by 23%, 30%, and 28%, respectively). Analysis of the enzyme kinetics indicated that the Vmax increased with little change in the Km with L-3,4-dihydroxyphenylalanine as substrate. The AADC activity in the striatum showed a time-dependent response after the administration of SCH 23390 and pimozide: the activity was increased within 30 min and the increases lasted 2-4 h. Inhibition of protein synthesis by cycloheximide (10 mg/kg, 0.5 h) had no effect on the striatal AADC activity or on the increases in striatal AADC activity produced by pimozide or SCH 23390. The results indicate that the increases in AADC activity induced by dopamine-receptor blockers are not due to de novo synthesis of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)