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1.
The aim of this study is to determine the effects of intrastriatal administration of MnCl2, on the extracellular levels of dopamine (DA) and metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in basal conditions and stimulated by depolarization with KCl and pargyline administration. Also, we studied the effect of MnCl2 on extracellular levels of l-Dopa in the presence of aromatic amino acid decarboxylase (AADC) inhibitor 3-hydroxybencilhydracine-HCl (NSD 1015). This study concluded that MnCl2, reduced the basal and K+-stimulated DA-release in striatum, without notably affecting the DOPAC and HVA levels. Intraperitoneal injection of pargyline increased striatal DA levels, decreasing DOPAC and HVA levels. The infusion of MnCl2 removed the increase in DA levels, without affecting DOPAC and HVA levels. Perfusion of NSD 1015 increased the extracellular levels of l-DOPA in striatum, and MnCl2 increased the effect of NSD1015 on l-Dopa.  相似文献   

2.
The administration of l-DOPA is the standard treatment for Parkinson’s disease (PD). However, the symptomatic relief provided by long-term administration may be compromised by l-DOPA-induced dyskinesia (LID) that presents as adverse fluctuations in motor responsiveness and progressive loss of motor control. In the later stages of PD, raphestriatal serotonin neurons compensate for the loss of nigrostriatal dopamine (DA) neurons by converting and releasing DA derived from exogenous l-DOPA. Since the serotonin system does not have an autoregulatory mechanism for DA, raphe-mediated striatal DA release may fluctuate dramatically and precede the development of LID. The 6-hydroxydopamine lesioned rats were treated with l-DOPA (6 mg/kg) and benserazide (15 mg/kg) daily for 3 weeks to allow for the development of abnormal involuntary movement score (AIMs). In rats with LID, chronic treatment with l-DOPA increased striatal DA levels compared with control rats. We also observed a relative increase in the expression of striatal l-amino-acid decarboxylase (AADC) in LID rats, even though tyrosine hydroxylase (TH) expression did not increase. The administration of l-DOPA also increased striatal serotonin immunoreactivity in LID rats compared to control rats. Striatal DA and 5-hydroxytryptamine (5-HT) levels were negatively correlated in l-DOPA-treated rats. These results of this study reveal that 5-HT contributes to LID. Striatal DA positively influences LID, while 5-HT is negatively associated with LID. Finally, we suggest that by strategic modification of the serotonin system it may be possible to attenuate the adverse effects of chronic l-DOPA therapy in PD patients.  相似文献   

3.
Behavioral and pharmacological effects of oral administration ofl-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected byl-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested thatl-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects ofl-deprenyl on behavior and cognitive function.  相似文献   

4.
Although they are effective at treating the motor impairments that are the core symptoms of Parkinson’s disease, current treatments, namely l-3,4-dihydroxyphenylalanine (l-DOPA), the gold standard medication and high-frequency stimulation of the subthalamic nucleus (HFS-STN), can lead to cognitive and mood alterations. Many of these side effects, such as depression, anxiety and sleep disturbances, could be related to abnormal functioning of the serotonergic system, but much basic research remains to be done. Molecular studies in humans and animal models of the disease have reported diverse drastic changes to the serotonergic system. It has also been shown that the serotonergic system both plays a major role in the mechanism of action of the current therapies and is altered by the therapies. It has been reported that HFS-STN decreases serotonin release in several regions, mostly via inhibition of serotonergic neuron activity. The involvement of serotonergic neurons in l-DOPA treatment is even more significant. First, serotonergic neurons, able to convert exogenous l-DOPA to dopamine, are a major site to release dopamine throughout the brain. Second, the substitution of serotonin by newly synthesized dopamine in serotonin neurons leads to acute and chronic alteration of serotonin release and metabolism. Therefore, both therapeutic approaches, via distinct mechanisms, decrease serotonergic system activity and, rather than alleviating cognitive or mood disorders, tend to aggravate them. Molecular strategies targeting the serotonergic system are being developed and could be decisive in limiting l-DOPA-induced dyskinesia, as well as mood and cognitive symptoms produced by antiparkinsonian therapies.  相似文献   

5.
Summary The turnover ofl-5-HTP,d-5-HTP and 5-HT in the exocrine pancreas have been studied by means of the fluorescence method ofFalck andHillarp. l- andd-5-HTP are easily taken up by the acinar cells, whereas 5-HT seems to pass into the cells only to a minor extent. After the administration ofl-5-HTP (and in some cases after 5-HT administration), specific fluorescence is seen in the form of apically located granules (probably identical with the zymogen granules) for a short period, which is prolonged, if the animals are pretreated with a MAO inhibitor. Decarboxylase inhibition prevents the appearance of these fluorescent granules. Administration ofd-5-HTP does not give rise to this granular fluorescence but to a diffuse fluorescence throughout the cells. Thus, there are reasons to assume that the granular fluorescence derives from 5-HT. The results obtained in this work correspond well with those from a similar study withl-DOPA and some of its analogues.abbreviations DOPA 3,4-dihydroxyphenylalanine - DA dopamine - NA noradrenaline - A adrenaline - 5-HTP 5-hydroxytryptophan - 5-HT 5-hydroxytryptamine - MAO monoamine oxidase This work was supported by grants from the Swedish Medical Research Council (B68-12X-712-03B and B68-14X-56-04B), the United States Public Health Service (06701-02) and the Faculty of Medicine, University of Lund, Lund, Sweden.  相似文献   

6.
The effects of limitating nitrogen-containing compounds in the medium and of adding the amino-acid analogues p-fluorophenylalanine and ethionine on both phenoloxidase activity and the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) are reported for cell suspension cultures of Mucuna pruriens. Nitrogen limitation of the cultures, or the addition of p-fluorophenylalanine or ethionine to the culture medium resulted in an increased phenoloxidase activity. There appeared to be an inverse relationship between phenoloxidase activity and the acccumulation of L-tyrosine into L-DOPA by alginate-entrapped cells occurred at a higher rate when phenoloxidase activity was increased.Abbreviations pFPA p-fluorophenylalanine - L-DOPA L-3,4-dihydroxyphenylalanine  相似文献   

7.
Serotonin-related disorders can be treated by manipulating serotonin synthesis with the serotonin precursor 5-hydroxytryptophan (5-HTP) or other pharmacological agents. The mollusc Tritonia diomedea is a model for investigating the effects of altering serotonin content on the functions of identified neurons. We used high-performance liquid chromatography and immunohistochemistry to examine the amount and localization of 5-HTP, serotonin, and the serotonin breakdown product 5-hydroxyindolacetic acid (5-HIAA) in the Tritonia brain after various pharmacological treatments. Exposure to 5-HTP (2 mM for 30 min-1 h) caused an immediate and massive increase in total 5-HTP content, which lasted more than 20 h, and the widespread appearance of 5-HTP immunoreactivity in neurons. Serotonin levels rose gradually, but only a restricted number of additional neurons displayed serotonin immunoreactivity. 5-HTP treatment also caused an increase in the total amount of 5-HIAA and the appearance of 5-HIAA immunoreactivity throughout the brain. Treatment with the synthesis cofactor tetrahydrobiopterin, the initial precursor tryptophan, or serotonin itself had no persistent effect on total serotonin content. The amino acid decarboxylase inhibitor hydroxybenzylhydrazine (NSD-1015) also had no effect on the total serotonin content, although it caused an accumulation of 5-HTP. Thus, serotonin levels in the brain of T. diomedea appear to be maintained by a homeostatic mechanism that can be disrupted by 5-HTP.  相似文献   

8.
Crocus sativus L., cultivated since ancient times as the source of saffron, is a triploid plant that can be propagated only via its corms which undergo a period of dormancy. Understanding the processes taking place in the corm is essential to preserve the plant and improve its quality. Color and taste being of prime importance in the quality of the saffron spice, knowledge on polyphenol oxidase (PPO) activity in the plant is of particular interest given the role of the enzyme in fruit and vegetable browning during processing and during the storage of processed food. In this paper, PPO activity was investigated for the first time in extracts obtained from dormant C. sativus L. corms. PPO activity was detectable using l-DOPA, pyrogallol, catechol or p-cresol as substrate, each being oxidized to its corresponding o-quinone; no activity was detectable with l-tyrosine, tyramine or phenol as substrate. Two pH optima, respectively at 4.5 and 6.7, were observed with all substrates and a third one, at 8.5, was found with l-DOPA and p-cresol. Kinetics parameters studied at pH 6.7 indicated the highest catalytic efficiency (in units mg−1 prot mM−1) with pyrogallol: 150, then catechol: 39, l-DOPA: 6.4 and p-cresol: 4.6. The enzymatic activity was inhibited by 50% in the presence of 0.22, 0.35, 0.5 and 0.7 mM kojic acid with, respectively, catechol, pyrogallol, p-cresol and l-DOPA as substrate. When stained for PPO activity, non-denaturing gel electropherograms of extract revealed three distinct bands, indicating the presence of multiple isoenzymes in dormant C. sativus L. corms.  相似文献   

9.
l-Aspartate (l-Asp) is an excitatory neurotransmitter in the central nervous system. In the present study, we demonstrate, for the first time, the presence of l-Asp in a particular neuronal cell class in the enteric nervous system (ENS). Scattered l-Asp-immunoreactive neuronal cell bodies and nerve fibers were found extensively in both the myenteric and submucosal plexus throughout the small and large intestines. Many l-Asp-immunoreactive nerve fibers, which originated from intrinsic nerve cell bodies, were found in the ganglia and interconnecting nerve bundles. Electron microscopy revealed that l-Asp-immunoreactive terminals frequently formed synaptic contacts with intrinsic nerve cells, suggesting that some l-Asp-immunoreactive neurons might function as interneurons. These results suggest that l-Asp-immunoreactive neurons play a significant role within the ENS to control intestinal functions. The presence of enteric l-Asp-immunoreactive neurons provides strong support for the proposal that l-Asp is a neuromodulator in the rat ENS.  相似文献   

10.
Primary neuronal cultures were made from eight-day-old embryonic chick telencephalon. Ten-day-old cultures were used to study the release ofd-[3H]aspartate andl-[3H]glutamate. Thed-[3H]aspartate release was stimulated by increasing potassium concentrations, but it was not calcium dependent. In contrast, the potassium dependentl-[3H]glutamate release was calcium dependent, and furthermorel-[3H]glutamate release was optimal at potassium concentrations<30 mM. The inhibitors of glutamate uptake, dihydrokainate and 1-aminocyclobutane-trans-1,3-dicarboxylic acid (CACB), also referred to as cis-1-aminocyclobutane-1,3-dicarboxylate, were used in the release experiments. Dihydrokainate had no effect on aspartate release, whereas CACB increased both the basal efflux ofd-[3H]aspartate and the potassium evoked release. CACB had no effect on the potassium stimulatedl-glutamate release. We believe thatl-glutamate is released mainly by a vesicular mechanism from the presumably glutamatergic neurons present in our culture.d-aspartate release observed by us, could be mediated by a transporter protein. The cellular origin of this release remains to be assessed.  相似文献   

11.
We investigated whether or not lettuce growth was inhibited by diffused L-3-(3,4-dihydroxyphenyl)alanine (L-DOPA), an allelochemical exuded from the roots of velvetbean (Mucuna pruriens (L.) DC. var. utilis) cultivars using a modified plant-box bioassay. For all the cultivars and one accession examined L-DOPA diffused from the roots and caused radicle and hypocotyl growth inhibition. A high correlation co-efficient (r = 0.838 to 0.982) was observed between L-DOPA concentration and lettuce seed sowing distance. L-DOPA diffused equally in all directions from roots at 0 mm position (close to root surface) in the plant-box, while the inhibition (%) of lettuce radicle growth gradually decreased with distance from the roots. For all cultivars the concentration of L-DOPA was significantly different at 0 mm position: being highest in cv. preta (167 g/ml) and lowest in cv. jaspeada and cv. ana (13 g/ml). The correlation between lettuce radicle growth inhibition and concentration of diffused L-DOPA was high (r = 0.856 to 0.966) in all cultivars and accession examined. However, the concentration of diffused L-DOPA did not correlate with the fresh weight concentration of L-DOPA measured in roots. The lettuce radicle growth inhibition from mucuna diffused L-DOPA was very similar that induced by synthetic L-DOPA, suggesting that diffused L-DOPA was the allelochemical responsible for growth inhibition.  相似文献   

12.
Four precursors (l-phenylalanine, l-tryptophan, cinnamic acid and emodin) and one signal elicitor (methyl jasmonate, MeJA) were added to liquid cultures of Hypericum perforatum L. to study their effect on production of hyperforin and hypericins (pseudohypericin and hypericin). The addition of l-phenylalanine (75 to 100 mg l−1) enhanced production of hypericins, but hyperforin levels were decreased. Hypericin, pseudohypericin and hyperforin concentrations were all decreased when l-tryptophan (25 to 100 mg l−1) was added to the medium. However, addition of l-tryptophan (50 mg l−1) with MeJA (100 μM) stimulated hyperforin production significantly (1.81-fold) and resulted in an increased biomass. Cinnamic acid (25, 50 mg l−1) and emodin (1.0 to 10.0 mg l−1) each enhanced hyperforin accumulation in H. perforatum, but did not affect accumulation of hypericins.  相似文献   

13.
Summary Thyroid parafollicular cells of normocalcemic and vitamin D2-treated rats were investigated by electron microscopy and with the histochemical fluorescence technique of Hillarp and Falck.Administration of high doses of vitamin D2 caused hypercalcemia and an extensive degranulation of the parafollicular cells.The formation and storage of monoamines in granulated and degranulated parafollicular cells was investigated by fluorescence microscopy after injection of monoamine precursors (DOPA, 5-HTP), alone or in combination with Ro 4-4602, nialamide or reserpine.No fluorescence was observed in parafollicular cells of untreated rats. l-DOPA and l-5-HTP (but not the corresponding D-amino acids) were taken up by a process closely linked to the decarboxylation of the amino acids to the corresponding amines (dopamine and 5-hydroxytryptamine). Treatment with vitamin D2 did not seem to affect the formation of amines in the parafollicular cells or the formation and storage of amines in other cell systems investigated. The amine itself (dopamine) was not taken up by the parafollicular cells.In normocalcemic rats, the amine formed was retained in the cytoplasm of the parafollicular cells by a partially reserpine-resistant mechanism. The storage of amines is concluded to occur in association with the calcitonin-containing granules.In parafollicular cells of vitamin D2-treated rats, a certain amount of amine was bound in the cytoplasm in the absence of typical granules. As a considerable amount of calcitonin is known to remain in the thyroid of vitamin D2-treated rats, the present observations may indicate an association between the amine and the polypeptide hormone calcitonin, whether the latter is confined to typical granules or not.The present study was supported by grants B72-12X-3352-02 and B72-14X-2207-06B from the Swedish Medical Research Council and by grants from Magnus Bergwall's Foundation, Gustav and Majen Lundgren's Foundation, Wilhelm and Martina Lundgren's Foundation and from the Faculty of Medicine, University of Göteborg, Sweden. For skilful technical assistance we are indebted to Mrs. Kirsten Collin and Mr. Pär-Anders Larsson.  相似文献   

14.
Intracellular precursor supply is a critical factor for amino acid productivity of Corynebacterium glutamicum. To test for the effect of improved pyruvate availability on l-lysine production, we deleted the aceE gene encoding the E1p enzyme of the pyruvate dehydrogenase complex (PDHC) in the l-lysine-producer C. glutamicum DM1729 and characterised the resulting strain DM1729-BB1 for growth and l-lysine production. Compared to the host strain, C. glutamicum DM1729-BB1 showed no PDHC activity, was acetate auxotrophic and, after complete consumption of the available carbon sources glucose and acetate, showed a more than 50% lower substrate-specific biomass yield (0.14 vs 0.33 mol C/mol C), an about fourfold higher biomass-specific l-lysine yield (5.27 vs 1.23 mmol/g cell dry weight) and a more than 40% higher substrate-specific l-lysine yield (0.13 vs 0.09 mol C/mol C). Overexpression of the pyruvate carboxylase or diaminopimelate dehydrogenase genes in C. glutamicum DM1729-BB1 resulted in a further increase in the biomass-specific l-lysine yield by 6 and 56%, respectively. In addition to l-lysine, significant amounts of pyruvate, l-alanine and l-valine were produced by C. glutamicum DM1729-BB1 and its derivatives, suggesting a surplus of precursor availability and a further potential to improve l-lysine production by engineering the l-lysine biosynthetic pathway. This study is dedicated to Prof. Dr. Hermann Sahm on the occasion of his 65th birthday.  相似文献   

15.
Utilization of d-amino acids being substrates of d-amino acid dehydrogenase of Salmonella typhimurium was examined. The experiments were done with wild type strains and the mutants dadA missing the enzyme activity and dadR in which its synthesis is released from catabolite repression. Growth on d-tryptophan, d-histidine and d-methionine used as precursors of the l-amino acids was faster when the respective auxotrophs carried dadR mutations. The dadR mutants grew faster when d-or l-alanine was present as a sole source of nitrogen. Experiments with d-amino acid dehydrogenase in vitro provided evidence that d-tryptophan is its substrate with a very low affinity to the dehydrogenase.  相似文献   

16.
The cell wall composition, the configuration of lactic acid produced from glucose under anaerobic conditions, the occurrence of fructose-1,6-diphosphate (FDP) activatedl-lactate dehydrogenase (l-LDH), and the esterase pattern were determined from more than 80 strains of coagulase-positive staphylococci isolated from man and animal. Strains isolated from man, swine, bovines and hares form a rather homogencous group. They exhibit a similar cell wall composition, produce predominantlyd,l-lactate and have a characteristic and simple esterase pattern. Coagulasepositive staphylococci isolated from dogs, horses, minks and pigeons are quite distinct from typicalStaphylococcus aureus strains. They exhibit a different cell wall composition, produce onlyl-lactate, possess anl-LDH which is specifically activated by FDP, and have a quite complex esterase pattern.List of Abbreviations BBP bromphenol blue - FDP fructose-1,6-diphosphate - d-LDH d-lactate dehydrogenase - l-LDH l-lactate dehydrogenase - NAD nicotinamide adenine dinucleotide  相似文献   

17.
Summary A series of mutants was isolated in Klebsiella pneumoniae strain 1033, among them mutants unable to grown on l-sorbose. Different R' plasmids carrying the sor genes and other surrounding chromosomal genes were also isolated. Each plasmid contained the structural genes sorA for an Enzyme II of the phosphoenolpyruvate-dependent carbohydrate: phosphotransferase system, sorD for a d-glucitol 6-phosphate dehydrogenase, sorE for an l-sorbose 1-phosphate reductase, and the corresponding regulator gene sorR. These structural genes are coordinately expressed and inducible by l-sorbose. Cis-dominant and pleiotropic mutations rendering the expression of the sor genes constitutive or eliminating it were isolated. Complementation of a series of mutations in Escherichia coli K12 and K. pneumoniae by various R' and F' plasmids and by P1 transduction in K. pneumoniae located the sor genes within the following gene sequence: rbs rha pfkA metB ppc argH ilv btuB rpoB metA ace sor pgi malB uvrA. The rbs-ilv gene loci tightly linked in E. coli K12 at 84 min, are separated in the map of K. pneumoniae 1033 and located at 86 and 89 min, respectively.  相似文献   

18.
The thermophilic phototrophic prokaryote, Chloroflexus aurantiacus was shown to contain high constitutive l-threonine (l-serine) deaminating activity. Separation of cellular proteins by DE 52-cellulose chromatography and by polyacrylamide gel electrophoresis with subsequent activity staining of the gels yielded two bands, one representing an isoleucine-sensitive, the other one an isoleucine-insensitive form of l-threonine dehydratase. Both enzymes had a molecular weight of 120,000 but were distinguished by their different affinities to the two substrates, l-threonine and l-serine.Abbreviations SDH l-serine dehydratase - TDH l-threonine dehydratase  相似文献   

19.
The yeast Schizosaccharomyces malidevorans utilizes l-malate when grown on glucose as the carbon source. A mutant of this yeast has been isolated which is dependent on the presence of both l-malate and glucose for growth. The mutant utilizes l-malate as rapidly as the wildtype and the utilization of glucose is greatly reduced. Other TCA cycle intermediates do not relieve the malate dependence.To John Ingraham whose pioneering work with malolactic bucteria made me curious enough about the field of nine microbiology to enter it and whose intense instruction in scientific method has made my continued pursuit of physiological and genetic questions a joy  相似文献   

20.
The phototrophic bacterium Rhodobacter capsulatus E1F1 assimilates ammonia and other forms of reduced nitrogen either through the GS/GOGAT pathway or by the concerted action of l-alanine dehydrogenase and aminotransferases. These routes are light-independent and very responsive to the carbon and nitrogen sources used for cell growth. GS was most active in cells grown on nitrate or l-glutamate as nitrogen sources, whereas it was heavily adenylylated and siginificantly repressed by ammonium, glycine, l-alanine, l-aspartate, l-asparagine and l-glutamine, under which conditions specific aminotransferases were induced. GOGAT activity was kept at constitutive levels in cells grown on l-amino acids as nitrogen sources except on l-glutamine where it was significantly induced during the early phase of growth. In vitro, GOGAT activity was strongly inhibited by l-tyrosine and NADPH. In cells using l-asparagine or l-aspartate as nitrogen source, a concerted induction of l-aspartate aminotransferase and l-asparaginase was observed. Enzyme level enhancements in response to nitrogen source variation involved de novo protein synthesis and strongly correlated with the cell growth phase.Abbreviations ADH l-alanine dehydrogenase - AOAT l-alanine:2-oxoglutarate aminotransferase - Asnase l-asparaginase - GOAT Glycine: oxaloacetate aminotransferase - GOGAT Glutamate synthase - GOT l-aspartate: 2-oxoglutarate aminotransferase - GS Glutamine synthetase - HPLC High-Pressure Liquid Chromatography - MOPS 2-(N-morpholino)propanesulfonic acid - MSX l-methionine-d,l-sulfoximine  相似文献   

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