Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DOPA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1977

An improved fluorimetric method for assay of dopa in urine and tissues and its use for determination of urinary dopa, at endogenous level, in different species.

An optimized fluorimetric method is presented which permits the analysis of DOPA in urine or tissues, at endogenous levels. A wide variety of eluates can be analyzed by applying the manual or the automated schedule. The automated manifold, developed for DOPA assay, may be used to estimate norepinephrine (NE) in other samples, by only changing the nature of reagents to be pumped. Amounts of DOPA as low as 0.3 ng/ml of eluate can be detected. Determinations of endogenous DOPA are reported in urinary samples of Humans, Rats, Dogs and Sheeps, and in brain of Rats. The pattern of changes in DOPA urinary excretion has been investigated as a function of time in Rats. Dietary influences have been studied in Man, Rat and Dog. It is concluded that the greatest part of free and conjugated DOPA excreted in urine of these animals has an endogenous origin.

Adult↗
PubMed1995

L-DOPA and psychosis: evidence for L-DOPA-induced increases in prefrontal cortex dopamine and in serum corticosterone.

L-DOPA can often induce psychotic reactions during treatment for Parkinson's disease. This study was undertaken to assess, in an animal model of Parkinson's disease, the impact of L-DOPA treatment on two potential biological risk factors for psychosis, namely, an increase in prefrontal cortex dopamine and an increase in the stress-related hormone corticosterone. Hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA) lesions which resulted in severe unilateral denervation of dopamine neurons were treated with either saline or 25 mg/kg L-DOPA methyl ester (with 2 mg/kg carbidopa). Serum L-DOPA concentrations were found to be positively and highly correlated with serum corticosterone, with medial prefrontal cortex dopamine and with the dopamine metabolite homovanillic acid. Serum L-DOPA, however, was found not to be correlated with serum or brain concentrations of serotonin, 5-hydroxyindoleacetic acid, or norepinephrine. These findings support the possibility that chronic L-DOPA treatment can expose parkinsonian patients to two significant risk factors for psychosis: 1) increased levels of prefrontal cortex dopamine, and 2) increased levels of serum corticosterone.

Animals↗
PubMed1983

Combined administration of direct dopamine receptor agonists and L-dopa does not interfere with utilization of exogenous L-dopa in rat corpus striatum.

The effect of combined administration of L-dopa with apomorphine or with bromocriptine on rat striatal concentrations of dopamine (DA), dihydroxyphenylacetic (DOPAC) and dopa was investigated. Injections of apomorphine or bromocriptine alone decreased striatal DOPAC levels indicating suppression of DA turnover in nigrostriatal terminals. The dopa-induced elevations in striatal concentrations of DA, DOPAC and dopa were similar among animals injected with L-dopa alone or in combination with apomorphine or bromocriptine. These findings suggest that although direct DA receptor agonists decrease striatal DA turnover, they do not interfere with utilization of exogenous L-dopa in striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Autocatalytic generation of dopa in the engineered protein R2 F208Y from Escherichia coli ribonucleotide reductase and crystal structure of the dopa-208 protein.

The mutant form Phe-208-->Tyr of the R2 protein of Escherichia coli ribonucleotide reductase contains an intrinsic ferric-Dopa cofactor with characteristic absorption bands at 460 and ca. 700 nm [Ormö, M., de Maré, F., Regnström, K., Aberg, A., Sahlin, M., Ling, J., Loehr, T. M., Sanders-Loehr, J., & Sjöberg, B. M. (1992) J. Biol. Chem. 267, 8711-8714]. The three-dimensional structure of the mutant protein, solved to 2.5-A resolution, shows that the Dopa is localized to residue 208 and that it is a bidentate ligand of Fe1 of the binuclear iron center of protein R2. Nascent apoR2 F208Y, lacking metal ions, can be purified from overproducing cells grown in iron-depleted medium. ApoR2 F208Y is rapidly and quantitatively converted to the Dopa-208 form in vitro by addition of ferrous iron in the presence of oxygen. Other metal ions (Cu2+, Mn2+, Co2+) known to bind to the metal site of wild-type apoR2 do not generate a Dopa in apoR2 F208Y. The autocatalytic generation of Dopa does not require the presence of a tyrosine residue at position 122, the tyrosine which in a wild-type R2 protein acquires the catalytically essential tyrosyl radical. It is proposed that generation of Dopa initially follows the suggested reaction mechanism for tyrosyl radical generation in the wild-type protein and involves a ferryl intermediate, which in the case of the mutant R2 protein oxygenates Tyr 208. This autocatalytic metal-mediated reaction in the engineered R2 F208Y protein may serve as a model for formation of covalently bound quinones in other proteins.

Apoproteins↗
PubMed1981

Inhibition of the renin-angiotensin-aldosterone system by L-dopa with and without inhibition of extracerebral dopa decarboxylase in man.

1. The present study was undertaken to investigate the possibility that central nervous system mono-aminergic pathways may play a role in the control of the renin-angiotensin-aldosterone system in man. 2. Eight normal subjects received in a randomized order placebo, L-dopa (500 mg, orally) and L-dopa (100 mg, orally) plus carbidopa (35 mg, orally) after pretreatment with carbidopa (50 mg every 6 h for four doses). 3. L-Dopa administration elicited a significant fall in plasma renin activity (PRA) (P less than 0.01 at 120, 150 and 180 min) and in plasma aldosterone levels (P less than 0.05 at 90, 120, 150 and 180 min); L-dopa plus carbidopa induced a decrease in PRA (P less than 0.05 at 120 and 150 min, P less than 0.01 at 180 min) and in plasma aldosterone concentration (P less than 0.05 at 30 and 60 min, P less than 0.01 at 90 and 120 min), in comparison with placebo administration; between-drugs analysis revealed no difference in the decreases in PRA and plasma aldosterone levels induced by the two regimens. 4. Since L-dopa, as well as L-dopa plus carbidopa, has been shown to augment catecholamine levels in the brain of various animal species, the present data suggest that in man PRA and plasma aldosterone concentration might be inhibited by increased central nervous system catecholamine levels.

Adult↗
PubMed1994

L-dopa increases nigral production of hydroxyl radicals in vivo: potential L-dopa toxicity?

Dopamine (DA) deficiency in Parkinson's disease is commonly treated with L-dihydroxyphenylalanine (L-dopa), the amino acid precursor to DA. L-dopa is neurotoxic in vitro and impairs survival of metabolically stressed neurons in vivo. We examined with microdialysis of substantia nigra in awake rats the local production of hydroxyl (OH) radicals before and after systemic L-dopa. We found a dose-dependent increase in OH radical output which paralleled the rate of dopa catabolism, was not blocked by deprenyl, and was increased further by acute inhibition of mitochondrial complex I activity. Following high L-dopa doses, catabolism of dopa-derived DA can exceed capacity of nigral mechanisms to reduce formation of or detoxify free radicals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

L-Dopa methyl ester--a candidate for chronic systemic delivery of L-Dopa in Parkinson's disease.

Continuous intravenous infusions of L-Dopa as a treatment for response swings in Parkinson's disease are limited by the insolubility and acidity of L-Dopa. Its methyl ester is a soluble neutral derivative that might be of benefit to these patients, and is examined in the present study in behavioural and biochemical animal models. On intraperitoneal or subcutaneous administration to mice L-Dopa methyl ester was equivalent to L-Dopa in reversing reserpine-induced akinesia and producing contraversive circling behaviour in rats with a 6-hydroxydopamine lesion of the medial forebrain bundle. On oral administration the methyl ester was more active. The administration of L-Dopa or the methyl ester produced equivalent changes in striatal and mesolimbic dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid metabolite levels. We suggest that systemic or subcutaneous infusion of L-Dopa methyl ester to patients who experience response fluctuations may provide a means of maintaining mobility.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Radical production during tyrosinase reaction, dopa-melanin formation, and photoirradiation of dopa-melanin.

It has been suggested that superoxide anion (O2-) may be produced during eumelanin formation and during the photoirradiation of eumelanin , but no direct evidence for this has yet been reported (although O2- production during photoirradiation of pheomelanin has been shown). In this report, the production of O2- was investigated during the formation and photoirradiation of dopa-melanin, a synthetic eumelanin . It was found that cytochrome c was reduced during the tyrosinase reaction and dopa-melanin formation in vitro; this reduction could not be inhibited by superoxide dismutase (SOD). When dopa-melanin was irradiated by UV radiation or by visible light, high nitroblue tetrazolium (NBT) reduction was observed; this reduction was proportional to the light energy and the amount of dopa-melanin. NBT reduction by visible light could be slightly inhibited by SOD, but a 12% decrease of NBT reduction by UV radiation could be shown with the addition of SOD. These observations indicate that some radicals were produced during the tyrosinase reaction and dopa-melanin formation. Further, when dopa-melanin was irradiated, radicals were also produced, some of which were thought to consist of O2-, but others were unknown.

Catechol Oxidase↗
PubMed1985

Carbidopa dosage modifies L-dopa induced side effects and blood levels of L-dopa and other amino acids in advanced parkinsonism.

Thirty-four patients with advanced Parkinson's disease showing intolerance to therapeutic doses of L-DOPA were treated with L-DOPA plus carbidopa at two different proportions. Ten patients preferred medication containing 10% carbidopa while 24 preferred 25% carbidopa. The increase of carbidopa reduced gastrointestinal disturbances and psychiatric side effects related to L-DOPA, but improvement of disability when measured according to objective tests was modest. Higher doses of carbidopa reduced peripheral DOPA metabolism and increased blood levels of tryptophan, 3-OM-DOPA and DOPA in relation to the administered dose.

Aged↗
PubMed1979

The effect of simultaneous administration of 3,4-dihydroxyphenylpyruvic acid and L-dopa on the bioavailability of L-dopa in rat and mouse.

In the rat, administration of 3-(3,4-dihydroxy)-L-phenylalanine (L-dopa) simultaneously with the corresponding alpha-keto acid, 3,4-dihydroxyphenylpyruvic acid (DHPPA), gives significantly higher concentrations of L-dopa in the serum and of dopamine and homovanillic acid in the brain than the same dose of L-dopa alone. Correspondingly, DHPPA potentiates the effect of L-dopa on the locomotor activity in reserpine-treated mice. DHPPA is postulated to increase the absorption of intact L-dopa from the gut by preventing the transamination reaction between L-dopa and the physiological alpha-keto acids.

Animals↗
PubMed1985

Effect of L-dopa with and without inhibition of extra cerebral dopa decarboxylase on gastric acid secretion and gastrin release in man.

The present study was undertaken to investigate the possibility that central nervous system monoaminergic pathways may play a role in the control of gastric acid and gastrin secretion in man. Submaximal pentagastrin stimulated (0.25 micrograms/kg/h) gastric acid secretion, as well as basal gastrin concentrations were studied in two groups of subjects. The first group received oral administration of placebo and the catecholamine precursor L-dopa (500 mg); the second group was treated with placebo and the association of L-dopa (100 mg) plus carbidopa (35 mg) after pretreatment with carbidopa (50 mg every six hours for four doses), a schedule which is known to increase brain catecholamine concentrations. In comparison with placebo, stimulated gastric acid secretion was reduced by L-dopa alone, whereas was not modified by L-dopa plus carbidopa. Basal gastrin concentrations were increased after L-dopa and after L-dopa plus carbidopa. These data show that basal gastrin concentration is raised by central catecholamine augmentation; but gastric acid secretion seems to be influenced by changes of peripheral catecholamine concentrations. It is suggested that dopamine and perhaps noradrenaline, but not adrenaline, are important in these effects.

Adult↗
PubMed1997

Effects of L-DOPA/carbidopa administration on the levels of L-DOPA, other amino acids and related compounds in the plasma, brain and heart of the rat.

Rats were treated intraperitoneally with a mixture of 250 mg/kg L-DOPA and 40 mg/kg carbidopa or with vehicle and sacrificed 30 min later. Plasma, heart and cortex, midbrain, brainstem and cerebellum were removed from each animal and assayed by HPLC for L-DOPA and a large number of amino acids and related amino compounds. L-DOPA levels increased from undetectable (<0.2 nmol/ml or g) to 1,146, 1,007, 399, 376, 368 and 850 nmol/ml or g in the above tissues. In addition, several amino compounds were significantly affected by L-DOPA/carbidopa (p < or = 0.01). Plasma concentrations of phosphoserine, oxidized glutathione, citrulline, phenylalanine, tyrosine and 1-methylhistidine increased and arginine, glutamic acid and lysine decreased. In the heart, concentrations of phosphoserine, taurine, reduced glutathione, threonine, serine, glutamine, glycine, alanine, valine, GABA, ethanolamine, ammonia and arginine decreased. In the cortex, camosine and homocarnosine increased. In the midbrain, valine increased and leucine, ornithine and oxidized glutathione decreased. In the cerebellum, citrulline increased. In the brainstem, threonine, serine, asparagine, glutamine, oxidized glutathione, alanine, and leucine decreased. In the brainstem, arginine was slightly decreased with a concomitant increase in citrulline (p < 0.05), indicative of nitrous oxide formation. These results show that administration of L-DOPA/ carbidopa not only raises dopamine levels but can also affect other biochemicals and that the observed changes in amino acids and related compounds can perhaps contribute to the beneficial and/or adverse effects of L-DOPA/carbidopa therapy of Parkinson's disease.

Amino Acids↗
PubMed1993

Comparison of striatal 18F-dopa uptake in adult-onset dystonia-parkinsonism, Parkinson's disease, and dopa-responsive dystonia.

We studied six patients with adult-onset dystonia-parkinsonism (DYS-P) with 18F-6-fluoro-dopa (18F-dopa) positron emission tomography and compared their influx constants (Ki values) with those of six patients with classical childhood-onset dopa-responsive dystonia (DRD), 12 age-matched Parkinson's disease (PD) patients without dystonia, and 21 normal controls. The DYS-P group had significantly reduced mean caudate (67% of normal) and putamen (45% of normal) 18F-dopa uptake. These Ki values were similar to mean caudate and putamen Ki values obtained for the PD group. In contrast, the DRD group showed minor reductions in mean caudate (9%) and putamen (18%) 18F-dopa uptake when compared with normals. The mean caudate:putamen Ki ratio was 1.7 in the DYS-P group and 2.1 in the PD group. In the DRD and normal groups, the caudate:putamen ratios were close to unity. The findings of this study are that adult-onset DYS-P targets the nigrostriatal dopaminergic projections in a pattern similar to PD, with the putamen being more affected. This provides support for the hypothesis that DYS-P may be a phenotypic variant of Lewy body disease. DYS-P seems distinct from childhood-onset DRD, in which striatal 18F-dopa uptake is either normal or only mildly reduced.

Adult↗
PubMed1999

The great DOPA mystery: the source and significance of DOPA in phase I melanogenesis.

One of the important characteristics of tyrosinase is the autocatalytic nature of the oxidation of natural monohydric phenol substrates, such as tyrosine. In vitro tyrosinase exhibits a lag phase in which the maximum velocity of oxidation is attained after a period of induction. This acceleration contrasts with the kinetics of dihydric phenol oxidation which exhibit conventional Michaelis-Menten kinetics. It has been known for half a century that DOPA is a co-factor in the oxidation of tyrosine and addition of a small amount of catechol reduces the length of the lag period. The significance of DOPA is in this action, and DOPA is known to be formed in phase I melanogenesis. Until recently there has been controversy regarding the source of the DOPA in the in vitro reaction system. Most investigators have favoured a mechanism based on the generation of DOPA by a direct hydroxylation of tyrosine. However, recent evidence has suggested that DOPA is indirectly derived by reduction of dopaquinone. In this communication the evidence for the indirect mechanism derived from the use of analogue substrates is reviewed.

Animals↗
PubMed1995

Comparative study of selegiline plus L-dopa-carbidopa versus L-dopa-carbidopa alone in the treatment of Parkinson's disease.

The long-term effect of selegiline (L-deprenyl) in the treatment of Parkinson's disease has not been clearly delineated. We report on a group of patients whose treatment was initiated with selegiline (n = 43) and then subsequently included L-dopa-carbidopa (Sinemet) and in whom an extended period of observation was carried out; they are compared to a group of patients whose treatment consisted of L-dopa-carbidopa alone (n = 39). In each, serial observations of the parkinsonian state and the response to treatment on a yearly basis for a period of 5 years were performed. No significant difference in the Hoehn-Yahr stage or in the motor subscores of tremor, rigidity, bradykinesia, and gait-posture was found between the two groups, nor was there a significant difference in the incidence of fluctuating responses or dyskinesias. The group that received combination therapy required less L-dopa than did the group that received L-dopa-carbidopa alone during the first 3 years of treatment and a similar trend was evident in years 4 to 5. We conclude that minimal benefits accrued to the parkinsonian patients from long-term use of selegiline. No clinical evidence to support the claim of "neuroprotective" properties was found. Selegiline's major usefulness is to modify the fluctuating therapeutic response seen with L-dopa-carbidopa.

Aged↗
PubMed1976

In vivo assessment of decarboxylase inhibition or potentiation: urinary dopamine and L-dopa output after L-dopa administration.

In the L-Dopa treated rat, a decreased urinary output of free and conjugated dopamine and an increase in free and conjugated L-Dopa excretion after administration of decarboxylase-inhibiting drugs provide a good in vivo index of Dopa decarboxylase inhibition. With the exception of free dopamine output, which showed an equivocal change, these measurements appear to provide a good yardstick of decarboxylase status in man also. Using this approach, it was not possible to find any evidence of facilitation of decarboxylase action, in L-Dopa-treated parkinsonians given pyridoxine supplements, to account for the ability of this compound to neutralize the beneficial effect of L-Dopa.

Animals↗
PubMed1990

Fast enzymatic preparation of L-dopa from tyrosine and molecular oxygen: a potential method for preparing [15O]L-dopa.

A fast, simple and inexpensive enzymatic preparation of 3,4-dihydroxyphenyl-L-alanine (L-DOPA) from molecular oxygen and tyrosine using mushroom tyrosinase is described. The theoretical incubation time for production of [15O]L-DOPA with maximal specific activity from [15O]O2 can be calculated to be about 3 min. In practice, using a specially-designed glass reaction chamber to facilitate the incorporation of gaseous molecular oxygen into L-DOPA with zero lag-time, a 3 min reaction with 1% oxygen in nitrogen results in the formation of approx. 3.9 mumols of L-DOPA, representing conversion of about 14% of the tyrosine substrate. Given access to a supply of [15O]O2, the method should be applicable to the preparation of [15O]L-DOPA for use as a PET tracer.

Levodopa↗
PubMed1989

DOPA, norepinephrine, and dopamine in rat tissues: no effect of sympathectomy on muscle DOPA.

We studied the effect of unilateral sympathectomy on rat quadriceps and gastrocnemius muscle concentrations of endogenous dihydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE) and assessed the relationships between these catecholamines in several rat tissues. Catecholamines were measured by reverse-phase high-performance liquid chromatography with electrochemical detection. Sympathectomy decreased NE and DA concentrations of muscles to approximately 10% of control values, whereas the DOPA concentration tended to increase. Relatively high concentrations of DOPA were found in the gastrointestinal tract, kidney, and spleen. No correlations were obtained between the tissue concentration of DOPA and NE. A DA-to-NE ratio approximately 1% was observed in liver, muscle, pancreas, spleen, and heart, whereas we found exponentially increasing DA values with increasing NE concentration in tissues obtained from stomach, small and large intestine, kidney, and lung. In conclusion, endogenous DOPA in muscle tissue is not located in sympathetic nerve terminals but probably in muscle cells. DA concentrations in the gastrointestinal tract and in the kidneys were greater than could be ascribed to its role as a precursor in the biosynthesis of NE.

Animals↗