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PubMed1990

Simultaneous measurement of L-dopa, its metabolites and carbidopa in plasma of parkinsonian patients by improved sample pretreatment and high-performance liquid chromatographic determination.

A procedure is described for the determination of L-3,4-dihydroxyphenylalanine (L-DOPA), its metabolites and carbidopa (CD) in plasma of Parkinsonian patients by high-performance liquid chromatography with dual working-electrode coulometric electrochemical detection. An efficient sample preparation scheme is presented for the isolation of L-DOPA, its metabolites and the catecholamines from the same plasma aliquot. After a simple deproteinization with methanol containing 2% of 0.5 M perchloric acid and evaporation of the solvent, L-DOPA, its metabolites and CD were separated with a 5-micron Nucleosil C18 column. Catecholamines were extracted from the supernatant of the deproteinized plasma by ion exchange on small columns and adsorption on alumina. Recoveries were close to 100% for L-DOPA, its metabolites and CD and 70% for catecholamines. The use of the same mobile phase for the concurrent assay of L-DOPA, its metabolites and catecholamines considerably increased the throughput of samples in the chromatographic system. The dual-electrode coulometric detector afforded peak identification by comparing current ratios. Monitoring of data from patients under L-DOPA therapy is reported.

Carbidopa↗
PubMed1998

DNA breakage by L-DOPA and Cu(II): breakage by melanin and bacteriophage inactivation.

We have previously shown that L-DOPA in the presence of Cu(II) caused DNA cleavage through the generation of reactive oxygen species such as the hydroxyl radical. Since L-DOPA is the precursor for the synthesis of melanin, we have studied the action of melanin on DNA in a similar reaction. In this paper, we show that melanin in the presence of Cu(II) also causes DNA strand breakage. However, the rate of such strand breakage is considerably less than l-DOPA. Melanin and L-DOPA are both capable of generating superoxide anion. Furthermore, the action of L-DOPA and Cu(II) on bacteriophage lambda reduces its viability. The results are discussed in relation to the putative role of L-DOPA-Cu(II) system as a source of endogenous generation of reactive oxygen species.

Bacteriophage lambda↗
PubMed2003

L-DOPA increases noradrenaline turnover in central and peripheral nervous systems.

The ability of L-3,4-dihydroxyphenylalanine (L-DOPA) to release noradrenaline (NA) from peripheral and CNS neurons was studied using isolated rat vas deferens and in vivo frontal cortex microdialysis. Application of L-DOPA (30 microM) to vas deferens increased basal NA efflux but not electrical field stimulation-evoked release of NA when the tissue was pretreated with an inhibitor of MAO-B (clorgyline 1 microM) or an inhibitor of MAO-A and MOA-B (AGN-1133 1 microM). No effect on NA efflux was seen when the tissue was treated with rasagiline (0.005 microM; selective inhibitor of MAO-B), but rasagiline, AGN-1133 and clorgyline increased basal efflux of dopamine (DA) following L-DOPA. In microdialysis experiments, systemic administration of L-DOPA/carbidopa combination (50/12 mg.kg(-1)) increased the efflux of 3,4-dihydroxyphenylglycol and 3-methoxy,4-hydroxyphenylglycol but reduced that of NA. Microdialysate levels of NA, however were increased following L-DOPA/carbidopa when desipramine (1 microM) was infused locally via the probe, or following systemic administration of yohimbine (2 mg.kg(-1)). The data are consistent with the hypothesis that administration of L-DOPA is followed by increased axoplasmatic levels of DA which release NA from storage sites into the free cytoplasmatic pool.

Animals↗
PubMed1990

Comparison between the L-DOPA histofluorescence procedure and the indirect immunofluorescence with anti-T6 and -HLA-DR monoclonal antibodies in visualizing Langerhans cells of human epidermis.

In order to assess the reliability of the L-DOPA histofluorescence (HF) procedure in visualizing the Langerhans cells (LC) of human epidermis, serial sections of human normal skin samples have been incubated with L-DOPA and alternatively processed for the L-DOPA HF and the indirect IF with anti-T6 and anti-HLA-DR monoclonal antibodies. Results demonstrated a good correlation of LC labelling; comparison between the number of L-DOPA positive (T6 positive and L-DOPA positive) HLA-DR positive dendritic cells did not show statistically significant differences. Therefore, the L-DOPA HF represents a valuable method for detecting LC in the human normal epidermis.

Adult↗
PubMed1997

L-tyrosine and nicotine induce synthesis of L-Dopa and norepinephrine in human lymphocytes.

Catecholamines (CA) were studied in peripheral human lymphocytes in basal conditions as well as after L-tyrosine and/or acetylcholine (ACh) stimulation. Nicotinic and muscarinic receptor activation and blockade were assessed. CA were determined after ultrasonic cell disruption in peripheral lymphocytes after incubation (1 h at 37 degrees C) with the chemicals employed. L-tyrosine significantly increased (P < 0.01) L-Dopa and norepinephrine (NE) content of lymphocytes. ACh in the low microM range did not modify, whereas ACh (60 microM) and (120 microM) significantly increased (P < 0.01), both L-Dopa and NE intracellular levels. L-tyrosine plus ACh (60 microM) or (120 microM) significantly increased (P < 0.01) intracellular L-Dopa and NE versus control, versus L-tyrosine alone and versus ACh alone. The increase was higher than the algebraic sum of the individual increases. Nicotine (250 microM), but not muscarine (50 microM), significantly increased L-Dopa and NE in lymphocytes. Tetraethylammonium (500 microM) (nicotinic blocker), but not atropine (100 microM) (muscarinic blocker), inhibited the ACh-mediated increase of intracellular L-Dopa and NE. These data show that lymphocyte synthesis of CA is under nicotinic control. Since intracellular L-Dopa after L-tyrosine plus ACh increased 6-fold versus basal, 2-fold versus L-tyrosine alone and 3-fold versus ACh alone, it is concluded that ACh might regulate CA synthesis in lymphocytes through an activation of the rate limiting enzyme tyrosine hydroxylase.

Acetylcholine↗
PubMed1997

Differential regional effects of long-term L-DOPA treatment on preproenkephalin and preprotachykinin gene expression in the striatum of 6-hydroxydopamine-lesioned rat.

The present study examined the effects of prolonged L-DOPA treatment (6 months) alone or in combination with unilateral 6-hydroxydopamine-induced lesion of the mesostriatal dopaminergic pathway on substance P and enkephalin mRNA expression in the rat neostriatum. This was done by means of quantitative in situ hybridization histochemistry. As reported previously, the unilateral dopaminergic lesion induced a significant and homogeneous decrease in striatal substance P mRNA expression and a marked increase in enkephalin mRNA expression in the ipsilateral neostriatum which was more pronounced in the dorsolateral than ventromedial part of the structure. Long-term L-DOPA treatment alone had no significant effects on the two striatal peptide mRNA levels. The chronic L-DOPA treatment in 6-hydroxydopamine-lesioned rats was found to partially reverse the lesion-induced down-regulation of substance P mRNA expression, without significantly affect the up-regulation of enkephalin when considering the neostriatum as a whole. Topographical analysis revealed that long-term L-DOPA treatment reversed, in fact, both post-lesional enkephalin and substance P responses to 6-hydroxydopamine lesion, in the ventromedial neostriatum, without significantly modified these peptide responses in the dorsolateral neostriatum. These findings provide new evidence that prolonged L-DOPA treatment differentially affects the post-lesional peptide responses in the ventromedial and dorsolateral parts of the neostriatum, suggesting regional cellular mechanisms in the neostriatum underlying the benefit and/or side-effects of L-DOPA treatment in parkinsonian patients.

Animals↗
PubMed1999

The evidence for tonic GABAergic regulation of basal L-DOPA release via activation of inhibitory GABA(A) receptors in the nucleus tractus solitarii of anesthetized rats.

We have proposed that DOPA is a neurotransmitter of the primary baroreceptor afferents terminating in the rat nucleus tractus solitarii (NTS). GABA is a putative inhibitory neuromodulator for baroreflex inputs in the NTS. Thus, GABA may inhibit DOPAergic transmission in the NTS. We tried to clarify whether basal DOPA release is inhibited by muscimol, a GABA(A) agonist, and facilitated by bicuculline, a GABA(A) antagonist, during microdialysis of the NTS in anesthetized rats. DOPA release was consistently detectable. Muscimol 10-100 microM perfused via probes gradually inhibited concentration-dependently DOPA release. Peak 30% inhibition occurred 2 h after perfusion. Muscimol (30 microM)-induced inhibition was antagonized by non-effective 10 microM bicuculline. Bicuculline (30 microM) elicited peak 30% facilitation of DOPA release 2 h after perfusion. Endogenous GABA seems to regulate tonically basal DOPA release via activation of inhibitory GABA(A) receptors in the rat NTS. These findings further support the above proposal.

Anesthesia↗
PubMed1978

Rapid procedure for chromatographic isolation of DOPA, DOPAC, epinephrine, norepinephrine and dopamine from a single urinary sample at endogenous levels.

A three-step procedure has been investigated to extract 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), epinephrine (E), norepinephrine (NE) and dopamine (DA) from a single urinary sample with the object of obtaining extracts pure enough for specific fluorimetric assay. The procedure described in this paper results from the combination of urine purification on an aluminum oxide column, separation by ion-exchange chromatography of the DOPA-DOPAC fraction from catecholamines, and ether isolation of DOPAC from DOPA. The whole procedure is rapid and easily performed in one work day. Extraction recoveries were 72.4 +- 3.5%, 76 +- 2%, 85.7 +- 3.3%, 85.6 +- 1.4% and 92.4 +- 5.5% for DOPA, DOPAC, E, NE and DA respectively (n=6). The lowest amounts of the five catechols that could be detected in urinary samples by a combination of this extraction procedure and the methods of assay used in our laboratory were 15 ng for DOPA, 40 ng for NE, 20 ng for E, 152 ng for DA and 2.95 micrograms for DOPAC. Urinary volumes convenient for accurate estimation of each compound were 20 ml for healthy human subjects. For pathological or pharmacological purposes, 5 ml of human urine were sufficient. The daily excretion of DOPA, DOPAC, E, NE and DA found by this procedure agrees with data obtained by other authors in healthy subjects. In pathological samples, our three-step procedure led to lower amounts than methods using alumina purification only. The discrepancies between the two methods are discussed in terms of development of internal standards, relative specificity of fluorimetric assays, values of blank eluates, and the possibility of interference from unknown abnormal body metabolites or pharmacological drugs not eliminated by a single-step alumina purification.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Simultaneous determination of L-dopa and 3-O-methyldopa in human platelets and plasma using high-performance liquid chromatography with electrochemical detection.

Various high-performance liquid chromatographic (HPLC) methods for the determination of plasma levels of L-dopa and of its metabolite, 3-O-methyldopa (3-OMD), have been previously described. In this study, we report a modification of these methods, that enables the assay of these two compounds in platelets and plasma obtained from the same sample of whole blood. Reversed-phase (RP) HPLC with electrochemical (coulometric) detection was used. The within-run and between-run coefficients of variations, for the two compounds, were less than 10%, in both platelets and plasma; the detection limits for platelet levels of L-dopa and 3-OMD were 2 and 6 ng/10(9) platelets, respectively. In plasma, the detection limits for L-dopa and 3-OMD were 1 and 3 ng/ml, respectively. The method is rapid and simple. When applied to a population of patients with Parkinson's disease under treatment with L-dopa, this method revealed detectable levels of L-dopa and 3-OMD in the platelets of all patients. The application of this technique may provide new insights into the pharmacokinetics of L-dopa in patients with Parkinson's disease.

Adult↗
PubMed1999

Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA.

Oxidative stress plays a central role in the pathogenesis of Parkinson's disease (PD). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pro-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, untreated PD patients and PD patients treated only with L-DOPA. We also measured platelet and plasma levels of L-DOPA, 3-O-methyldopa (the long-lasting metabolite of the drug), and dopamine. We found that isolated platelets of treated PD patients form higher amounts of 2,3-dihydroxybenzoate, an index of hydroxyl radical generation, than platelets of controls or untreated patients. In treated patients, platelet levels of 2,3-dihydroxybenzoate were positively correlated with platelet levels of L-DOPA, 3-O-methyldopa, and with the score of disease severity. Disease severity was correlated with platelet and plasma levels of L-DOPA, as well as with the daily intake of the drug. No significant differences in platelet levels of cytosolic and mitochondrial isoforms of the antioxidant enzyme superoxide dismutase were found between PD patients, either treated or untreated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients.

Antiparkinson Agents↗
PubMed2003

Denervation and repeated L-DOPA induce a coordinate expression of the transcription factor NGFI-B in striatal projection pathways in hemi-parkinsonian rats.

Repeated intermittent administration of L-DOPA in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway results in a progressive increase of contraversive circling behavior. In this study, we have investigated the effects of denervation and repeated L-DOPA administration on the expression of the nuclear receptor nerve growth factor inducible-B (NGFI-B) in striatal output pathways of unilaterally 6-OHDA-lesioned rats. The denervation process induced an increase of NGFI-B and enkephalin (ENK) mRNA levels and the increase of NGFI-B took place predominantly in ENK-containing cells. The percentage of cells colocalizing NGFI-B and dynorphin (DYN) was significantly reduced. Repeated L-DOPA treatment increased the striatal level of DYN mRNA but it further reduced the percentage of NGFI-B/DYN double-labeled cells. On the intact side, repeated L-DOPA treatment increased NGFI-B expression in both striatal subpopulations. Additional acute studies were performed in normal rats to determine the role of the denervation process in the coordinate expression of NGFI-B in striatal subpopulations. A combination of selective D(1) and D(2) agonists induced an important increase of striatal NGFI-B expression selectively in DYN-containing neurons. These results demonstrate that the denervation process causes a differential regulation of NGFI-B in the two striatal output pathways which is further exacerbated by L-DOPA treatment. These molecular changes in response to dopamine depletion and dopamine replacement therapy may contribute to the long-term effects of L-DOPA and to the development of behavioral sensitization.

Animals↗
PubMedDate not supplied

Effects of dopamine and alpha-2 adrenoreceptor blockade on L-dopa and cholecystokinin-induced gastroprotection.

Dopamine and cholecystokinin have been colocalized in neurons and represent endogenous enteric neurotransmitters. Both peptides possess potent protective actions against gastric injury when given exogenously. This study was undertaken in conscious female rats to test the hypothesis that cholecystokinin may exert its protective actions via release of dopamine. Experiments were designed to ascertain whether L-dopa, a dopamine precursor, could prevent gastric injury with the same degree of efficacy as cholecystokinin and to determine what role alpha-2 adrenoreceptors and dopamine receptors play in mediating the protective actions of these peptides. Intraperitoneal administration of L-dopa (1 to 25 mg/kg) in a dose-dependent manner prevented the type of macroscopic injury to the acid-secreting portion of the stomach that is caused by 1 ml of orogastric acidified ethanol (150 mmol/L hydrochloric acid/50% ethanol), an effect corroborated by histologic examination. Administration of either the alpha-2 adreno-receptor antagonist yohimbine (0.1 to 1.0 mg/kg) or the dopamine receptor antagonist haloperidol (1 to 5 mg/kg) caused a partial reversal of L-dopa-induced protection but not the protective actions of subcutaneous cholecystokinin (100 microg/kg). Simultaneous administration of both receptor antagonists had an additive effect and completely reversed the protective actions of L-dopa. The dopamine precursor L-dopa was just as effective in maintaining the integrity of the gastric epithelium in the face of a damaging insult as the gut peptide cholecystokinin. However, the data indicate that L-dopa initiates its protective actions through activation of both alpha-2 adrenoreceptors and dopamine receptors, whereas the protective effects of cholecystokinin are elicited by means of a different mechanism.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2005

Protein resistance of titanium oxide surfaces modified by biologically inspired mPEG-DOPA.

In the present study, we have utilized X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (ELM), and optical waveguide lightmode spectroscopy (OWLS) to examine the surface adsorption and protein resistance behavior of bio-inspired polymers consisting of poly(ethylene glycol) (PEG) conjugated to peptide mimics of mussel adhesive proteins. Peptides containing up to three residues of 3,4-dihydroxyphenylalanine (DOPA), a key component of mussel adhesive proteins, were conjugated to monomethoxy-terminated PEG polymers. These mPEG-DOPA polymers were found to be highly adhesive to TiO2 surfaces, with quantitative XPS analysis providing useful insight into the binding mechanism. Additionally, the antifouling properties of immobilized PEG were reflected in the excellent resistance of mPEG-DOPA-modified TiO2 surfaces to protein adsorption. Measurements of mPEG-DOPA and human serum adsorption were related in terms of ethylene glycol (EG) surface density and serum mass adsorbed and demonstrated a threshold of approximately 15-20 EG/nm2, above which substantially little protein adsorbs. With respect to surface density of adsorbed PEG and the associated nonfouling behavior of the adlayers, strong parallels exist between the nonfouling properties of the surface-bound mPEG-DOPA polymers and PEG polymers immobilized to surfaces using other approaches. Peptide anchors containing three DOPA residues resulted in PEG surface densities higher than those achieved using several existing PEG immobilization strategies, suggesting that peptide mimics of mussel adhesive proteins may be useful for achieving high densities of protein-resistant polymers on surfaces.

Biomimetic Materials↗
PubMed2006

Synthesis and characterization of water-soluble and photostable L-DOPA dendrimers.

A small drug molecule, L-DOPA, was converted into well-defined dendritic macromolecules. Their monodisperse nature was shown by NMR, MALDI-TOF-MS, and PAGE. A third-generation L-Dopa dendrimer contained 30 L-Dopa residues, which made up its core, branches, and periphery. Individual L-Dopa moieties in the dendrimer were connected to one another via hydrolyzable diester linkages. These Dopa dendrimers showed a 20-fold increase in aqueous solubility and enhanced photostability in solutions over L-Dopa under identical conditions.

Dendrimers↗
PubMed2000

Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs.

PURPOSE: To study the utility of the nasal route for the systemic delivery of L-dopa using water soluble prodrugs of L-dopa and to examine if this delivery method will result in preferential delivery to the CNS. METHODS: Several alkyl ester prodrugs of L-dopa were prepared and their physicochemical properties were determined. In vitro hydrolysis rate constants in buffer, rat plasma, rat brain homogenate, rat CSF, and rat nasal berfusate were determined by HPLC. In vivo nasal experiments were carried out in rats. Levels of L-dopa and dopamine in plasma, CSF, and olfactory bulb were determined using HPLC method with electrochemical detection. RESULTS: All the prodrugs showed improved solubility and lipophilicity with relatively fast in vitro conversion in rat plasma. Absorption was fast following nasal delivery of the prodrugs with bioavailability around 90%. Dopamine plasma levels did not change significantly following nasal administration of the butyl ester prodrug. Olfactory bulb and CSF L-dopa concentration were higher following nasal delivery of the butyl ester prodrug compared to an equivalent intravenous dose. CONCLUSIONS: Utilization of water soluble prodrugs of L-dopa via the nasal route in the treatment of Parkinson's disease may have therapeutic advantages such as improved bioavailability, decreased side effects, and potentially enhanced CNS delivery.

Administration, Intranasal↗
PubMed1999

Differential effects of chemical sympathectomy on expression and activity of tyrosine hydroxylase and levels of catecholamines and DOPA in peripheral tissues of rats.

Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4-dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA. Presence of chromaffin cells or neuronal cell bodies in these latter tissues, indicated by consistent expression of TH mRNA, explained the relative resistance of these tissues to 6-OHDA. Stomach also showed consistent expression of TH mRNA before, but not after 6-OHDA, suggesting that catecholamine synthesizing cells in gastric tissue are sensitive to the toxic effects of 6-OHDA. Tissue concentrations of DOPA were mainly unaffected by 6-OHDA, indicating that much of the DOPA in peripheral tissues is synthesized independently of local TH or sympathetic innervation. The differential effects of chemical sympathectomy on tissue catecholamines, DOPA, TH mRNA and TH activity demonstrate that these variables are not simple markers of sympathetic innervation or catecholamine synthesis. Other factors, including presence of neuronal cell bodies, parenchymal chromaffin cells, non-neuronal sites of catecholamine synthesis and alternative sources of tissue DOPA, must also be considered when tissue catecholamines, DOPA and TH are examined as markers of sympathetic innervation and local catecholamine synthesis.

Animals↗
PubMed1998

Evidence for the involvement of P-glycoprotein on the extrusion of taken up L-DOPA in cyclosporine A treated LLC-PK1 cells.

1. The present work has examined the effects of short- (30 min) and long-term (14 h) exposure to cyclosporine A (CsA) on the uptake of L-DOPA, its decarboxylation to dopamine and the cellular extrusion of taken up L-DOPA and of newly-formed amine in monolayers of LLC-PK1 cells. 2. In the presence of benserazide (50 microM), L-DOPA was rapidly accumulated in LLC-PK1 cells (cultured in collagen-treated plastic) attaining equilibrium at 30 min of incubation. Non-linear analysis of the saturation curves revealed a Km of 113+/-16 microM and a Vmax of 5581+/-297 pmol mg(-1) protein 6 min(-1). 3. In the absence of benserazide, LLC-PK1 cells incubated with increasing concentrations of L-DOPA (10 to 500 microM) for 6 min accumulate newly-formed dopamine by a saturable process with apparent Km and Vmax values of 31+/-6 microM and 1793+/-91 pmol mg(-1) protein 6 min(-1), respectively. The fractional outflow of newly-formed dopamine was found to be 20%. Up to 200 microM of intracellular newly-formed dopamine, the outward transfer of the amine was found to be a non-saturable process. 4. Short-term exposure to CsA (0.3, 1.0 and 3.0 microg ml(-1)) was found not to change the intracellular concentrations of newly-formed dopamine, but increased the levels of dopamine in the incubation medium (143% to 224% increase) and the total amount of dopamine formed (31% to 59% increase). Long-term exposure to CsA (0.03 to 3.0 microg ml(-1)) reduced the total amount of dopamine (15% to 39% reduction) and the intracellular levels of the amine (11% to 56% reduction), without changing dopamine levels in the incubation medium. Both short- and long-term exposure to CsA resulted in a concentration-dependent increase in the fractional outflow of newly-formed dopamine. 5. Short-term exposure to CsA (3.0 microg ml(-1)) reduced the apical extrusion of intracellular L-DOPA by 15% (P<0.05), whereas long-term exposure to CsA reverted this effect and decreased its intracellular availability (15% reduction; P<0.05). 6. Detection of P-glycoprotein activity was carried out by measuring verapamil- or UIC2-sensitive rhodamine 123 accumulation. Both UIC2 (3 microg ml(-1)) and verapamil (25 microM) significantly increased the accumulation of rhodamine 123 in LLC-PK1 cells. A 30 min exposure to CsA was found not to affect the accumulation of rhodamine 123 in the presence of verapamil (25 microM), whereas a 14 h exposure to CsA was found to reduce the accumulation of rhodamine 123. 7. In conclusion, the increase and the reduction in the formation of dopamine after short- and long-term exposure to CsA, respectively, correlate with the effects of the immunosuppressant on the apical cell extrusion of taken up L-DOPA, suggesting the involvement of P-glycoprotein. The effects of CsA on the fractional outflow of newly-formed dopamine appear to be mediated by a different mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1975

The reciprocal exclusion by L-dopa (L-3,4-dihydroxyphenylalanine) and L-tyrosine of their incorporation as single units into a soluble rat brain protein.

Several compounds, structurally and metabolically related to phenylalanine and tyrosine, were tested for their effects on the incorporations of phenylalanine and tyrosine as single units into a protein of the soluble subcellular fraction of rat brain. Of the compounds tested, only L-dopa (L-3,4-dihydroxyphenylalanine) inhibited these incorporations. Further, L-dopa was incorporated into a protein of the same fraction in such a way that it excluded the incorporation of tyrosine as a single unit. Conversely, tyrosine inhibited and excluded the incorporation of L-dopa. The incorporation of L-dopa required ATP (apparent Km = 0.23mM), KCl (apparent Km = 20mM) and MgCl2 (optimal concentration range, 5-16mM). These requirements were similar to those previously determined for the incorporation of tyrosine and phenylalanine. The inactivation rate of the enzymic systems for L-tyrosine and L-dopa incorporations, when kept at 37 degrees C, was the same for both amino acids (half-life = 80 min). It is suggested that the acceptor for the incorporation of dopa is the same as that for the incorporation of tyrosine.

Adenosine Triphosphate↗