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Published: 4 June 2021
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1

Wolfovitz, Efrat, Ehud Grossman, Carol J. Folio, Harry R. Keiser, Irwin J. Kopin, and David S. Goldstein. "Derivation of Urinary Dopamine from Plasma Dihydroxyphenylalanine in Humans." Clinical Science 84, no. 5 (May 1, 1993): 549–57. http://dx.doi.org/10.1042/cs0840549.

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1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spillover) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 μg min−1 kg−1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenylacetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 ± (SEM) 0.01 to 0.14 ± 0.03 nmol/min, t = 2.80, P <0.02] and dopamine (from 1.03 ± 0.19 to 1.30 ± 0.28 nmol/min, t = 2.35, P <0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged. 4. Renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounted for virtually all the urinary excretion of endogenous dopamine, but for only a minor portion of the excreted endogenous dihydroxyphenylacetic acid. 5. We conclude that in humans: (1) circulating dihydroxyphenylalanine is the main source of urinary dopamine but only a minor source of urinary dihydroxyphenylacetic acid; and (2) increased spillover of endogenous dihydroxyphenylalanine does not account for the increased excretion of these compounds during salt loading.
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2

Matsushita, Naoko, Yoshimi Misu, and Yoshio Goshima. "In vivo antagonism of the behavioral responses to L-3-,4-dihydroxyphenylalanine by L-3-,4-dihydroxyphenylalanine cyclohexyl ester in conscious rats." European Journal of Pharmacology 605, no. 1-3 (March 2009): 109–13. http://dx.doi.org/10.1016/j.ejphar.2008.12.032.

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3

Adamiec, J., K. Cejpek, J. Rössner, and J. Velíšek. "Novel Strecker degradation products of tyrosine and dihydroxyphenylalanine." Czech Journal of Food Sciences 19, No. 1 (February 7, 2013): 13–18. http://dx.doi.org/10.17221/6568-cjfs.

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Tyrosine was oxidised with either potassium peroxodisulphate or glyoxal. Volatile reaction products were isolated and analysed by GC/FID and GC/MS, derivatised with diazomethane and analysed by the same methods. Eight reaction products were identified. The major products were the expected Strecker aldehyde (4-hydroxyphenylacetaldehyde) and its lower homologue 4-hydroxybenzaldehyde. They were followed by 1-(4-hydroxyphenyl)-3-propionaldehyde, phenylacetaldehyde, benzaldehyde, phenol, 4-hydroxybenzoic, and benzoic acid. Analogously, the oxidation of 3,4-dihydroxyphenylalanine yielded the corresponding Strecker aldehyde (3,4-dihydroxyphenylacetaldehyde), its lower homologue 3,4-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic, 3,4-dihydroxyphenylacetic, and caffeic acid. An identification of these oxidation products of tyrosine and 3,4-dihydroxyphenylalanine assumes homolytic cleavage of the Strecker aldehydes and a recombination of free radicals formed by this cleavage. As minor products, six O- and N-heterocyclic compounds arose in systems containing glyoxal (pyrazine, methyl- and ethylpyrazine, 3-furancarbaldehyde, 5-methyl-2-furancarbaldehyde, 2-pyrrolcarbaldehyde).
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4

GOLDSTEIN, DAVID S. "Plasma 3, 4-Dihydroxyphenylalanine (Dopa) and Catecholamines in Neuroblastoma or Pheochromocytoma." Annals of Internal Medicine 105, no. 6 (December 1, 1986): 887. http://dx.doi.org/10.7326/0003-4819-105-6-887.

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5

Chen, Lisha, Fengxia Chang, Lingchen Meng, Meixian Li, and Zhiwei Zhu. "A novel electrochemical chiral sensor for 3,4-dihydroxyphenylalanine based on the combination of single-walled carbon nanotubes, sulfuric acid and square wave voltammetry." Analyst 139, no. 9 (2014): 2243–48. http://dx.doi.org/10.1039/c4an00098f.

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6

Xiong, Xiong, Ding Hai Li, and Yue Feng Wang. "Differences in Thermal Stability and Surface Morphology of Dopa and Dopamine Graft Compound." Advanced Materials Research 641-642 (January 2013): 951–54. http://dx.doi.org/10.4028/www.scientific.net/amr.641-642.951.

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L-3, 4-Dihydroxyphenylalanine(DOPA) has a unique catechol moiety found in adhesive proteins in marine organisms, such as mussels and polychaete, which results in strong adhesion in aquatic conditions. Conventional efforts incorporating DOPA into polymer is grafting methacrylate anhydride. For this reason, we synthesized the new catechol intermediate N-methacryloyl 3,4-dihydroxyl-phenylamine and analyzed the surface morphology and thermal stability of it.
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7

Tamura, Sadaaki, Teruhiko Nitoda, and Isao Kubo. "Effects of Salicylic Acid on Mushroom Tyrosinase and B16 Melanoma Cells." Zeitschrift für Naturforschung C 62, no. 3-4 (April 1, 2007): 227–33. http://dx.doi.org/10.1515/znc-2007-3-412.

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Abstract Salicylic acid slightly inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by mushroom tyrosinase noncompetitively without being oxidized. In contrast, 4-hydroxybenzoic acid did not inhibit this enzymatic oxidation if a longer reaction time was observed, although it suppressed the initial rate of the oxidation to a certain extent. Neither acid showed noticeable effects on cultured murine B16-F10 melanoma cells except weak cytotoxicity.
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8

Forster, Christine, George Naik, and Paul W. Armstrong. "Noradrenaline biosynthesis and metabolism during development and recovery from pacing-induced heart failure in the dog." Canadian Journal of Physiology and Pharmacology 72, no. 1 (January 1, 1994): 45–49. http://dx.doi.org/10.1139/y94-008.

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We have modified an assay utilizing ion-pair high-performance liquid chromatography with electrochemical detection to measure dihydroxyphenylalanine and dyhydroxyphenylglycol simultaneously with noradrenaline. We measured these agents at control, 1 and 3 weeks following the onset of rapid ventricular pacing, as well as 4 weeks after the cessation of a 3-week period of pacing. Our findings were as follows. Plasma noradrenaline increased significantly at 1 week and increased further after 3 weeks of pacing (control, 202 ± 16; 1 week, 528 ± 62; 3 weeks, 750 ± 139 pg∙mL−1). Plasma dihydroxyphenylalanine did not change throughout, while plasma dihydroxyphenylglycol was significantly elevated at 3 weeks (513 ± 48 vs. 388 ± 35 pg∙mL−1 for the control). Four weeks after discontinuation of pacing, all parameters did not differ from the control. These results imply that during the development of heart failure, the rise in circulating noradrenaline does not reflect simply an increase in catecholamine synthesis, but that there are more dynamic changes associated with noradrenaline spillover, uptake, and metabolism.Key words: heart failure, dihydroxyphenylglycol, sympathetic nervous activity, noradrenaline.
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9

Nakajima, Naoko, Syuntaro Hiradate, and Yoshiharu Fujii. "Characteristics of Growth Inhibitory Effect of L-3, 4-Dihydroxyphenylalanine (L-DOPA) on Cucumber Seedlings." Journal of Weed Science and Technology 44, no. 2 (1999): 132–38. http://dx.doi.org/10.3719/weed.44.132.

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10

Nakamura, Shinichi, Yoshio Goshima, and Yoshimi Misu. "Transmitter-like release of endogenous 3, 4-dihydroxyphenylalanine from the rat striatum investigated by microdialysis." Neuroscience Research Supplements 14 (January 1991): S147. http://dx.doi.org/10.1016/s0921-8696(06)80429-9.

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11

Visanji, N. P., S. H. Fox, T. H. Johnston, M. J. Millan, and J. M. Brotchie. "α1-Adrenoceptors Mediate Dihydroxyphenylalanine-Induced Activity in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Lesioned Macaques." Journal of Pharmacology and Experimental Therapeutics 328, no. 1 (October 27, 2008): 276–83. http://dx.doi.org/10.1124/jpet.108.144097.

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12

Goldstein, D. S., J. Vernikos, C. Holmes, and V. A. Convertino. "Catecholaminergic effects of prolonged head-down bed rest." Journal of Applied Physiology 78, no. 3 (March 1, 1995): 1023–29. http://dx.doi.org/10.1152/jappl.1995.78.3.1023.

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Prolonged head-down bed rest (HDBR) provides a model for examining responses to chronic weightlessness in humans. Eight healthy volunteers underwent HDBR for 2 wk. Antecubital venous blood was sampled for plasma levels of catechols [norepinephrine (NE), epinephrine, dopamine, dihydroxyphenylalanine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid] after supine rest on a control (C) day and after 4 h and 7 and 14 days of HDBR. Urine was collected after 2 h of supine rest during day C, 2 h before HDBR, and during the intervals 1–4, 4–24, 144–168 (day 7), and 312–336 h (day 14) of HDBR. All subjects had decreased plasma and blood volumes (mean 16%), atriopeptin levels (31%), and peripheral venous pressure (26%) after HDBR. NE excretion on day 14 of HDBR was decreased by 35% from that on day C, without further trends as HDBR continued, whereas plasma levels were only variably and nonsignificantly decreased. Excretion rates of dihydroxyphenylglycol and dihydroxyphenylalanine decreased slightly during HDBR; excretion rates of epinephrine, dopamine, and dihydroxyphenylacetic acid and plasma levels of catechols were unchanged. The results suggest that HDBR produces sustained inhibition of sympathoneural release, turnover, and synthesis of NE without affecting adrenomedullary secretion or renal dopamine production. Concurrent hypovolemia probably interferes with detection of sympathoinhibition by plasma levels of NE and other catechols in this setting. Sympathoinhibition, despite decreased blood volume, may help to explain orthostatic intolerance in astronauts returning from spaceflights.
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13

Shimizu, T., N. Takeda, and S. Yagi. "Levels of Biogenic Amines in the Brain during Pupal and Adult Development of the Silkworm, Bombyx mori." Zeitschrift für Naturforschung C 52, no. 3-4 (April 1, 1997): 279–82. http://dx.doi.org/10.1515/znc-1997-3-424.

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AbstractLevels of a wide range of biogenic amines and related metabolites were determined in the brain of the silk­ worm, Bomby mori, during pupal and adult development using a three-dimensional HPLC system with multiple coulometric electrochemical detection.In the brain of the female adults, metabolic pathways such as tyrosine (TYR-4)->dihydroxyphenylalanine (L -DOPA)-dopamine (DA), TYR-4->tyramine (TYRA), and tryptophan (TRP)->5-hydroxytryptamine (5-HT) were identified. At this stage, 3,4-dihydroxyphenyleth-ylene (DOPAC) was also detected. Metabolic pathways of biogenic amines in the brain from pupal to adult stages are discussed.
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14

Zhang, Fuping, Shuping Bi, Feng Liu, and Ningsheng Bian. "Indirect Differential Pulse Voltammetric Determination of Aluminum Biological Samples in the Presence of 3, 4-Dihydroxyphenylalanine." Analytical Letters 33, no. 2 (January 2000): 209–19. http://dx.doi.org/10.1080/00032710008543047.

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15

Nurdoğan; BOZOĞLU, TOPAL. "Determination of l-dopa (l-3, 4-dihydroxyphenylalanine) content of some faba bean (vicia faba l.) genotypes." Tarım Bilimleri Dergisi 22, no. 2 (2016): 145–51. http://dx.doi.org/10.1501/tarimbil_0000001376.

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16

Takahama, Umeo, and Takayuki Oniki. "3, 4-Dihydroxyphenylalanine is oxidized by phenoxyl radicals of hydroxycinnamic acid esters in leaves ofVicia faba L." Journal of Plant Research 111, no. 4 (December 1998): 487–94. http://dx.doi.org/10.1007/bf02507783.

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17

Kano, Yoshihiro, Fumio Otsuka, Masaya Takeda, Jiro Suzuki, Kenichi Inagaki, Tomoko Miyoshi, Manabu Miyamoto, Hiroyuki Otani, Toshio Ogura, and Hirofumi Makino. "Regulatory Roles of Bone Morphogenetic Proteins and Glucocorticoids in Catecholamine Production by Rat Pheochromocytoma Cells." Endocrinology 146, no. 12 (December 1, 2005): 5332–40. http://dx.doi.org/10.1210/en.2005-0474.

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We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.
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18

Takahama, Umeo, and Kunijiro Yoshitama. "Hydroxycinnamic acid esters enhance peroxidase-dependent oxidation of 3, 4-dihydroxyphenylalanine. differences in the enhancement among the esters." Journal of Plant Research 111, no. 1 (March 1998): 97–100. http://dx.doi.org/10.1007/bf02507155.

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19

Ikeda, Hitoshi, Shiro Matsuyama, Norio Suzuki, Atsushi Takahashi, and Minoru Kuroiwa. "3, 4-Dihydroxyphenylalanine (DOPA) Decarboxylase Deficiency and Resultant High Levels of Plasma DOPA and Dopamine in Unfavorable Neuroblastoma." Hypertension Research 18, SupplementI (1995): S209—S210. http://dx.doi.org/10.1291/hypres.18.supplementi_s209.

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20

Speck, Ana E., Aderbal S. Aguiar, Samira G. Ferreira, Henrique B. Silva, Ângelo R. Tomé, Paula Agostinho, Rodrigo A. Cunha, and Rui D. Prediger. "Exercise decreases aberrant corticostriatal plasticity in an animal model of l-DOPA-induced dyskinesia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 320, no. 4 (April 1, 2021): R541—R546. http://dx.doi.org/10.1152/ajpregu.00295.2020.

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Physical exercise attenuates the development of l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID) in 6-hydroxydopamine-induced hemiparkinsonian mice through unknown mechanisms. We now tested if exercise normalizes the aberrant corticostriatal neuroplasticity associated with experimental murine models of LID. C57BL/6 mice received two unilateral intrastriatal injections of 6-hydroxydopamine (12 μg) and were treated after 3 wk with l-DOPA/benserazide (25/12.5 mg/kg) for 4 wk, with individualized moderate-intensity running (60%–70% V̇o2peak) or not (untrained). l-DOPA converted the pattern of plasticity in corticostriatal synapses from a long-term depression (LTD) into a long-term potentiation (LTP). Exercise reduced LID severity and decreased aberrant LTP. These results suggest that exercise attenuates abnormal corticostriatal plasticity to decrease LID.
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21

Melega, William P., Milton M. Perlmutter, Andre Luxen, Charna H. K. Nissenson, Scott T. Grafton, Sung-Cheng Huang, Michael E. Phelps, and Jorge R. Barrio. "4-[18F]Fluoro-L-m-Tyrosine: An L-3,4-Dihydroxyphenylalanine Analog for Probing Presynaptic Dopaminergic Function with Positron Emission Tomography." Journal of Neurochemistry 53, no. 1 (July 1989): 311–14. http://dx.doi.org/10.1111/j.1471-4159.1989.tb07331.x.

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22

Norouzian, Dariush, Azim Akbarzadeh, Saeed Mirdamadi, Shohreh Khetami, and Ali Farhanghi. "Immobilization of Mushroom Tyrosinase by Different Methods in Order to Transform L-Tyrosine to L-3, 4 Dihydroxyphenylalanine (L-dopa)." Biotechnology(Faisalabad) 6, no. 3 (June 15, 2007): 436–39. http://dx.doi.org/10.3923/biotech.2007.436.439.

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23

Trejo-Gonzalez, Augusto, and Herlinda Soto-Valdez. "Partial Characterization of Polyphenoloxidase Extracted from `Anna' Apple." Journal of the American Society for Horticultural Science 116, no. 4 (July 1991): 672–75. http://dx.doi.org/10.21273/jashs.116.4.672.

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Polyphenoloxidase (PPO) was studied in extracts from `Anna' apples (Malus domestica Borkh.) produced under the desert conditions of the state of Sonora, Mexico. A crude extract of PPO was prepared in phosphate buffer from an acetone powder of pulp from ripe apples. Optimum conditions for enzyme activity were pH 5.36 at 35C. Specificity toward substrates, in order of decreasing activity, was 4-methylcatechol, chlorogenic acid, catechol, caffeic acid, and 3,4-dihydroxyphenylalanine. Activation energy for the reaction with 4-methylcatechoI was 6543 J·mol-1 (1563 cal·mol-1). The PPO from `Anna' was similar to that described from other apple cultivars, except that it was more thermostable between 35 and 60C. A single peak of PPO activity was achieved by hydrophobic chromatography of the crude extract, resulting in a 300-fold purification. `Anna' apples contained high levels of phenolic substances, 1.16% on a fresh-weight basis. The high phenolic content and PPO thermostability help explain the browning susceptibility of `Anna' apples during postharvest handling.
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24

Fukushima, Akiyoshi, Hiroaki Hase, and Koshi Saito. "Further studies on the adsorption of plant phenols by synthetic polymers." Acta Societatis Botanicorum Poloniae 58, no. 4 (2014): 583–92. http://dx.doi.org/10.5586/asbp.1989.045.

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Pyrocatechol, catechol, caffeic acid, chlorogenic acid, safflor yellow A, safflor yellow B, precarthamin and carthamin were effectively adsorbed by insoluble polyvinyl-N-pyr­rolidone (PVP) in a neutral buffer solution. These eight phenols also bound with Amberlite XAD resins, however, the rate was found to be far less efficient than that of PVP. The average rate of the phenol binding was calculated as following order (%): PVP (42.7), Amberlite XAD-2 (16.6), Amberlite XAD-4 (10.1), Amberlite XAD-7 (13.0), Amberlite XAD-8 (17.7). No 3,4-dihydroxyphenylalanine was adsorbed by PVP, while the O-dihydroxylic acid could be removed by Amberlite XAD-4, XAD-7 and XAD-8. Data from using different weights of the test polymers showed that the rate of the phenol adsorption rose in proportion to each increasing amount of the adsorbents. PVP also admittedly maintained its predominent capacity for phenol binding over that of each member of the Amberlite resins.
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25

Arung, Enos Tangke, Keisuke Yoshikawa, Kuniyoshi Shimizu, and Ryuichiro Kondo. "The effect of chlorophorin and its derivative on melanin biosynthesis." Holzforschung 59, no. 5 (September 1, 2005): 514–18. http://dx.doi.org/10.1515/hf.2005.085.

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Abstract By means of bioassay-guided fractionation using mushroom tyrosinase, a geranylated stilbene, chlorophorin, was characterized as the principal tyrosinase inhibitor in the heartwood of Chlorophora excelsa (Moraceae). It inhibited the oxidation of L-tyrosine and DL-3,4-dihydroxyphenylalanine (DL-DOPA) due to mushroom tyrosinase and melanin biosynthesis on B16 melanoma cells. Chlorophorin, which is a slight yellowish compound, has previously been reported as an unstable compound in light. On the basis of this finding, a chlorophorin derivative [4-(3″,7″-dimethyloctyl)-2′,3,4′,5-tetrahydroxydihydrostilbene; hexahydrochlorophorin] which is colorless, obtained by the hydrogenation of chlorophorin with Pd/C, was also tested to develop a superior material for practical use. Hexahydrochlorophorin showed more potent inhibitory activity on tyrosinase and melanin biosynthesis, and lower cytotoxicity towards B16 melanoma cells than chlorophorin.
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26

GILLY, WM F., and MARY T. LUCERO. "Behavioral Responses to Chemical Stimulation of the Olfactory Organ in the Squid Loligo Opalescens." Journal of Experimental Biology 162, no. 1 (January 1, 1992): 209–29. http://dx.doi.org/10.1242/jeb.162.1.209.

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Behavioral experiments were carried out on restrained, but otherwise fully active, squid to test the chemoreceptive capabilities of the olfactory organ. Specific chemical substances stimulated high-pressure jet escape responses when ejected from a small pipette into the area immediately around the olfactory organ. These included squid ink and L-Dopa (3,4 dihydroxyphenylalanine) as well as agents that block voltage-dependent potassium channels, such as quaternary ammonium ions and 4-aminopyridine. Experiments designed to map chemosensitivity spatially identified the olfactory organ as the receptive site. Unilateral application of a topical local anesthetic to an olfactory organ selectively and reversibly abolished responsiveness on the treated side only. The olfactory organ can thus mediate detection of water-borne chemicals. This detection, in turn, is linked to motor control pathways involved in initiating escape-jetting behavior.
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27

Nelson, James T., Jaeheon Lee, James W. Sims, and Eric W. Schmidt. "Characterization of SafC, a Catechol 4-O-Methyltransferase Involved in Saframycin Biosynthesis." Applied and Environmental Microbiology 73, no. 11 (April 20, 2007): 3575–80. http://dx.doi.org/10.1128/aem.00011-07.

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ABSTRACT Members of the saframycin/safracin/ecteinascidin family of peptide natural products are potent antitumor agents currently under clinical development. Saframycin MX1, from Myxococcus xanthus, is synthesized by a nonribosomal peptide synthetase, SafAB, and an O-methyltransferase, SafC, although other proteins are likely involved in the pathway. SafC was overexpressed in Escherichia coli, purified to homogeneity, and assayed for its ability to methylate a variety of substrates. SafC was able to catalyze the O-methylation of catechol derivatives but not phenols. Among the substrates tested, the best substrate for SafC was l-dihydroxyphenylalanine (l-dopa), which was methylated specifically in the 4′-O position (k cat/Km = 5.5 × 103 M−1 s−1). SafC displayed less activity on other catechol derivatives, including catechol, dopamine, and caffeic acid. The more labile l-5′-methyldopa was an extremely poor substrate for SafC (k cat/Km = ∼2.8 × 10−5 M−1 s−1). l-Dopa thioester derivatives were also much less reactive than l-dopa. These results indicate that SafC-catalyzed 4′-O-methylation of l-dopa occurs prior to 5′-C-methylation, suggesting that 4′-O-methylation is likely the first committed step in the biosynthesis of saframycin MX1. SafC has biotechnological potential as a methyltransferase with unique regioselectivity.
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28

Pangestiningsih, TW, T. Susmiati, and H. Wijayanto. "Kandungan L-3, 4-dihydroxyphenylalanine Suatu Bahan Neuroprotektif pada Biji Koro Benguk (Mucuna pruriens) Segar, Rebus, dan Tempe (L-3,4-DIHYDROXYPHENYLALANINE CONTENT AS A NEUROPROTECTIVE MATERIAL ON FRESH, COOKED AND FERMENTED OF KORO BENGUK (MUCUNA PRURIENS) BEANS)." Jurnal Veteriner 18, no. 1 (April 12, 2017): 116–20. http://dx.doi.org/10.19087/jveteriner.2017.18.1.116.

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29

Barrio, Jorge R., Sung-Cheng Huang, Dan-Chu Yu, William P. Melega, Javier Quintana, Simon R. Cherry, Andrew Jacobson, Mohammad Namavari, Nagichettiar Satyamurthy, and Michael E. Phelps. "Radiofluorinated L-m-Tyrosines: New In-Vivo Probes for Central Dopamine Biochemistry." Journal of Cerebral Blood Flow & Metabolism 16, no. 4 (July 1996): 667–78. http://dx.doi.org/10.1097/00004647-199607000-00018.

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In this work, we introduce 6-[18F]fluoro-L- m-tyrosine (6-FMT) and compare its in-vivo kinetic and biochemical behaviors in monkeys and rodents with those of 4-FMT and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3- O-methylation, offer a nonpharmacological alternative to the use of catechol- O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essentially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and rodents, these new radiofluorinated m-tyrosine analogs accumulate selectively in striatal structures and allow for the detection of additional innervation sites (e.g., brain stem) rich in aromatic amino acid decarboxylase. Biochemical analyses in rodents and monkeys revealed the specificity of their central and peripheral metabolism. Molecular and enzymatic mechanisms involved in their retention in central brain structures are consistent with involvement of dopaminergic neurons. The high signal-to-noise ratios observed make these radiofluorinated m-tyrosine analogs outstanding candidates for probing the integrity of central dopaminergic mechanisms in humans.
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30

Kim, Jang Hoon, Sunggun Lee, Saerom Park, Ji Soo Park, Young Ho Kim, and Seo Young Yang. "Slow-Binding Inhibition of Tyrosinase by Ecklonia cava Phlorotannins." Marine Drugs 17, no. 6 (June 16, 2019): 359. http://dx.doi.org/10.3390/md17060359.

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Tyrosinase inhibitors improve skin whitening by inhibiting the formation of melanin precursors in the skin. The inhibitory activity of seven phlorotannins (1–7), triphlorethol A (1), eckol (2), 2-phloroeckol (3), phlorofucofuroeckol A (4), 2-O-(2,4,6-trihydroxyphenyl)-6,6′-bieckol (5), 6,8′-bieckol (6), and 8,8′-bieckol (7), from Ecklonia cava was tested against tyrosinase, which converts tyrosine into dihydroxyphenylalanine. Compounds 3 and 5 had IC50 values of 7.0 ± 0.2 and 8.8 ± 0.1 μM, respectively, in competitive mode, with Ki values of 8.2 ± 1.1 and 5.8 ± 0.8 μM. Both compounds showed the characteristics of slow-binding inhibitors over the time course of the enzyme reaction. Compound 3 had a single-step binding mechanism and compound 5 a two-step-binding mechanism. With stable AutoDock scores of −6.59 and −6.68 kcal/mol, respectively, compounds 3 and 5 both interacted with His85 and Asn260 at the active site.
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31

Bozoğlu, Hatice, and Merve Bezmen. "Determination of the L-DOPA (L-3, 4-Dihydroxyphenylalanine) Content in Faba Bean (Vicia faba L.) Flowers and Faba Bean Flower Tea." Turkish Journal of Agriculture - Food Science and Technology 9, no. 4 (April 24, 2021): 733–39. http://dx.doi.org/10.24925/turjaf.v9i4.733-739.4078.

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This study aimed to determine the L-DOPA content in the flowers of some different faba bean genotypes and determine the L-DOPA levels in tea prepared from flowers. The experiment was carried out under the ecological conditions in Samsun by the Black Sea with 15 genotypes using a randomized complete block design in three replications. The flowers were harvested three times and the number of flowers and flower yields were determined. The L-DOPA content of the flower and flower tea were determined using HPLC. Different solvents were used to extract the L-DOPA from the faba bean flowers. As a result of the HPLC analyses, the highest L-DOPA yield was determined to be in the tea samples brewed with hot water. It was found statistical differences between genotypes in the second and third harvests for the number of flowers in the plant and the total number of flowers. Dry flower yields ranged from 11.33 to 37.78 kg da−1 while L-DOPA levels were 6.2 to 9.17 g 100g−1 in dry flowers and 6.69 to 9.23 g 100g−1 in infused tea. The study concluded that flower tea of faba bean can be investigate for medicinal purposes and that L-DOPA in the plant can be extracted by brewing without requiring any solvent. This shows that L-DOPA is in a salt form within the plant.
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32

Giuri, Demetra, Nicola Zanna, and Claudia Tomasini. "Low Molecular Weight Gelators Based on Functionalized l-Dopa Promote Organogels Formation." Gels 5, no. 2 (May 14, 2019): 27. http://dx.doi.org/10.3390/gels5020027.

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We prepared the small pseudopeptide Lau-l-Dopa(OBn)2-d-Oxd-OBn (Lau = lauric acid; l-Dopa = l-3,4-dihydroxyphenylalanine; d-Oxd = (4R,5S)-4-methyl-5-carboxyl-oxazolidin-2-one; Bn = benzyl) through a number of coupling reactions between lauric acid, protected l-Dopa and d-Oxd with an excellent overall yield. The ability of the product to form supramolecular organogels has been tested with different organic solvents of increasing polarity and compared with the results obtained with the small pseudopeptide Fmoc-l-Dopa(OBn)2-d-Oxd-OBn. The mechanical and rheological properties of the organogels demonstrated solvent-dependent properties, with a storage modulus of 82 kPa for the ethanol organogel. Finally, to have a preliminary test of the organogels’ ability to adsorb pollutants, we treated a sample of the ethanol organogel with an aqueous solution of Rhodamine B (RhB) for 24 h. The water solution slowly lost its pink color, which became trapped in the organogel.
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33

Chen, Shuang Kou, Jian Fang Zhu, Wen Zhang Huang, Bai He, Li Jun Xiang, and Tai Gang Zhou. "Research Progress on Adhesion Mechanism of Marine Organism." Advanced Materials Research 781-784 (September 2013): 840–46. http://dx.doi.org/10.4028/www.scientific.net/amr.781-784.840.

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Marine adhesion organism includes biological mucosa such as marine bacteria, diatom, etc. and large adhesion organism such as mussel, barnacle, etc. Researches and analysis on adhesion mechanism of adhesion organism show that adhesion marine bacteria in biological mucosa will secrete protein-containing Polysaccharide polymer (PAVE) which can adhere to all kinds of surfaces. The reason is that in these secretions there is 3, 4-dihydroxyphenylalanine (DOPA) which is very viscous. Analysis on mussel, a large adhesion organism, shows that it is of super viscosity, which may result from its special molecular structure and the interaction way with substrates, and interstrand crosslink mediated by DOPA. DOPA plays an important role in this process. For marine bacteria and mussel, their viscosity is correlated with the generation and cross-linking of DOPA. On one hand, DOPA can enhance the viscosity of adhesion organism; on the other hand, it can improve the internal cohesion through cross-linking.
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34

Holten-Andersen, N., and J. H. Waite. "Mussel-designed Protective Coatings for Compliant Substrates." Journal of Dental Research 87, no. 8 (August 2008): 701–9. http://dx.doi.org/10.1177/154405910808700808.

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The byssus of marine mussels has attracted attention as a paradigm of strong and versatile underwater adhesion. As the first of the 3,4-dihydroxyphenylalanine (Dopa)-containing byssal precursors to be purified, Mytilus edulis foot protein-1 (mefp-1) has been much investigated with respect to its molecular structure, physical properties, and adsorption to surfaces. Although mefp-1 undoubtedly contributes to the durability of byssus, it is not directly involved in adhesion. Rather, it provides a robust coating that is 4–5 times stiffer and harder than the byssal collagens that it covers. Protective coatings for compliant tissues and materials are highly appealing to technology, notwithstanding the conventional wisdom that coating extensibility can be increased only at the expense of hardness and stiffness. The byssal cuticle is the only known coating in which high compliance and hardness co-exist without mutual detriment; thus, the role of mefp-1 in accommodating both parameters deserves further study.
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35

Grossman, Ehud, Aaron Hoffman, Peter C. Chang, Harry R. Keiser, and David S. Goldstein. "Increased spillover of dopa into arterial blood during dietary salt loading." Clinical Science 78, no. 4 (April 1, 1990): 423–29. http://dx.doi.org/10.1042/cs0780423.

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1. We measured urinary excretion rates of dopamine (3,4-dihydroxyphenethylamine) and dopa (3,4-dihydroxyphenylalanine) and the spillover rate of dopa into arterial blood during dietary salt loading in conscious Dahl salt-sensitive and salt-resistant rats with intact or denervated kidneys. 2. Dopa spillover was calculated from the steady-state clearance of intravenously infused l-[3H]dopa and arterial levels of endogenous dopa. 3. Daily excretion rates of dopa and dopamine increased by about sixfold during salt loading in both rat strains. Bilateral renal denervation delayed these increases and the natriuretic responses. 4. During dietary salt loading, dopa spillover increased to approximately the same extent as simultaneously measured dopamine excretion. 5. The results suggest that increases in urinary excretion of dopamine during dietary salt loading can be accounted for by increases in the release of dopa into the bloodstream and that the renal nerves contribute to the dopa and dopamine excretory responses.
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36

Jaiwal, Ranjana, and C. M. Chaturvedi. "Four Hour Temporal Relation of 5-HTP and L-DOPA Induces Inhibitory Responses in Recrudescing Gonad of Indian Palm Squirrel (Funambulus pennantii)." ISRN Endocrinology 2013 (July 1, 2013): 1–5. http://dx.doi.org/10.1155/2013/206876.

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Daily injections of L-dihydroxyphenylalanine (L-DOPA, dopamine precursor) given 4 h after 5-hydroxytryptophan (5-HTP, serotonin precursor) induced inhibitory responses in recrudescing gonad (in the first week of December) of Indian palm squirrel, a seasonally breeding subtropical animal. Other temporal relations (L-DOPA given at 0, 8, 12, 16, and 20 h after 5-HTP administration) did not show any effect on the recrudescing gonad. This inhibitory effect of 4 h was evident under short day length (6 : 18) group but was masked by the increasing day length of nature (NDL, late December onwards) and increased photoperiod of long day group (16 : 8). It is apparent that seasonal testicular recrudescence of Indian palm squirrel during short day length by 4 h relation of 5-HTP and L-DOPA is not a pharmacological effect but actually is an alteration of seasonality in this annually breeding mammal. It seems that endogenous mechanism controlling seasonal testicular recrudescence of Indian palm squirrel is reset by timed daily injections of these neurotransmitter drugs. It is suggested that in spite of different environmental factors (photoperiod, humidity, etc.) used by different species to time their annual reproduction, basic mechanism of seasonality appears to be the same, that is, the temporal synergism of neurotransmitter activity.
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37

Hsu, Albert, Daniel M. Togasaki, Erwan Bezard, Pierre Sokoloff, J. William Langston, Donato A. Di Monte, and Maryka Quik. "Effect of the D3 Dopamine Receptor Partial Agonist BP897 [N-[4-(4-(2-Methoxyphenyl)piperazinyl)butyl]-2-naphthamide] on l-3,4-Dihydroxyphenylalanine-Induced Dyskinesias and Parkinsonism in Squirrel Monkeys." Journal of Pharmacology and Experimental Therapeutics 311, no. 2 (June 29, 2004): 770–77. http://dx.doi.org/10.1124/jpet.104.071142.

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38

Bräutigam, Christa, Ron A. Wevers, Riet J. T. Jansen, Jan A. M. Smeitink, Johanneke F. de Rijk-van Andel, Fons J. M. Gabreëls, and Georg F. Hoffmann. "Biochemical hallmarks of tyrosine hydroxylase deficiency." Clinical Chemistry 44, no. 9 (September 1, 1998): 1897–904. http://dx.doi.org/10.1093/clinchem/44.9.1897.

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Abstract We report the biochemical hallmarks of tyrosine hydroxylase deficiency with emphasis on reliable diagnostic strategies of four new cases of an inborn error of tyrosine hydroxylase (TH). Three of our patients from different parts of the Netherlands were found homozygous for a mutation in exon 6 (G698A) of the TH gene, and one patient was found compound heterozygous for the same mutation and an additional mutation in exon 3. The first clinical symptoms of hypokinesia, rigidity of arms and legs and axial hypotonia, developed between 3 and 7 months of age. Cerebrospinal fluid investigations revealed a characteristic metabolite constellation in every case: low homovanillic acid (HVA) and 3-methoxy-4-hydroxy-phenylethyleneglycol concentrations in the presence of normal reference range 5-hydroxyindolacetic acid concentrations. Strict adherence to a standardized lumbar puncture protocol and adequate age-related reference values are essential for diagnosis of this “new” treatable neurometabolic disorder. Urinary measurements of HVA, vanillylmandelic acid, and catecholamines can lead to false-negative conclusions. All patients showed a remarkable clinical improvement on a low dose of l-dihydroxyphenylalanine/(S)-2-(3,4-dihydroxybenzyl)-2-hydrazinpropionic acid. During treatment, cerebrospinal fluid HVA, and 3-methoxy-4-hydroxy-phenylethyleneglycol increased substantially.
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39

Huot, Philippe, Tom H. Johnston, Tessa Snoeren, James B. Koprich, Michael P. Hill, Susan H. Fox, and Jonathan M. Brotchie. "Use of catechol-O-methyltransferase inhibition to minimize L-3,4-dihydroxyphenylalanine-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque." European Journal of Neuroscience 37, no. 5 (January 3, 2013): 831–38. http://dx.doi.org/10.1111/ejn.12093.

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40

Goldstein, David S., Robin Stull, Graeme Eisenhofer, and John R. Gill. "Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans." Clinical Science 76, no. 5 (May 1, 1989): 517–22. http://dx.doi.org/10.1042/cs0760517.

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1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown. 2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week. 3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation. 4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.
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41

Rubira, Rafael Jesus Gonçalves, Sabrina Alessio Camacho, Cibely Silva Martin, Jorge Ricardo Mejía-Salazar, Faustino Reyes Gómez, Robson Rosa da Silva, Osvaldo Novais de Oliveira Junior, Priscila Alessio, and Carlos José Leopoldo Constantino. "Designing Silver Nanoparticles for Detecting Levodopa (3,4-Dihydroxyphenylalanine, L-Dopa) Using Surface-Enhanced Raman Scattering (SERS)." Sensors 20, no. 1 (December 18, 2019): 15. http://dx.doi.org/10.3390/s20010015.

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Detection of the drug Levodopa (3,4-dihydroxyphenylalanine, L-Dopa) is essential for the medical treatment of several neural disorders, including Parkinson’s disease. In this paper, we employed surface-enhanced Raman scattering (SERS) with three shapes of silver nanoparticles (nanostars, AgNS; nanospheres, AgNP; and nanoplates, AgNPL) to detect L-Dopa in the nanoparticle dispersions. The sensitivity of the L-Dopa SERS signal depended on both nanoparticle shape and L-Dopa concentration. The adsorption mechanisms of L-Dopa on the nanoparticles inferred from a detailed analysis of the Raman spectra allowed us to determine the chemical groups involved. For instance, at concentrations below/equivalent to the limit found in human plasma (between 10−7–10−8 mol/L), L-Dopa adsorbs on AgNP through its ring, while at 10−5–10−6 mol/L adsorption is driven by the amino group. At even higher concentrations, above 10−4 mol/L, L-Dopa polymerization predominates. Therefore, our results show that adsorption depends on both the type of Ag nanoparticles (shape and chemical groups surrounding the Ag surface) and the L-Dopa concentration. The overall strategy based on SERS is a step forward to the design of nanostructures to detect analytes of clinical interest with high specificity and at varied concentration ranges.
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42

Hurley, M. J., P. H. Patel, M. J. Jackson, L. A. Smith, S. Rose, and P. Jenner. "Striatal leucine-rich repeat kinase 2 mRNA is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned common marmosets (Callithrix jacchus) with l-3, 4-dihydroxyphenylalanine methyl ester-induced dyskinesia." European Journal of Neuroscience 26, no. 1 (July 3, 2007): 171–77. http://dx.doi.org/10.1111/j.1460-9568.2007.05638.x.

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43

Grossman, Ehud, Aaron Hoffman, Ines Armando, Zaid Abassi, Irwin J. Kopin, and David S. Goldstein. "Sympathoadrenal contribution to plasma dopa (3,4-dihydroxyphenylalanine) in rats." Clinical Science 83, no. 1 (July 1, 1992): 65–74. http://dx.doi.org/10.1042/cs0830065.

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1. To determine the sources of dopa (3,4-dihydroxyphenylalanine) in plasma, we measured regional arteriovenous differences, tissue concentrations and urinary excretion of dopa during systemic intravenous infusions of I-[3H]dopa into anaesthetized intact rats and rats pretreated with the sympathetic neurotoxin, 6-hydroxydopamine. 2. In intact rats, large arteriovenous increments in plasma dopa concentrations were noted in the femoral (47%) and adrenal (141%) beds, with a small arterial-portal venous increment (11%), whereas in the kidney there was a substantial (47%) arteriovenous decrement in plasma dopa levels. Skeletal muscle appeared to be a major source of dopa in arterial plasma. 3. Treatment with 6-hydroxydopamine abolished the afferent-efferent increment of plasma dopa concentrations in the femoral bed. The arteriovenous decrement of plasma dopa concentrations in the kidney was preserved, and the arteriovenous increment in the adrenal bed was decreased by about half. Arterial plasma dopa levels fell by 41%. 4. Regional extraction percentages of I-[3H]dopa were used to estimate the clearances and rates of appearance (spillovers) of dopa in plasma. Dopa spillover was detected in the femoral, renal, splanchnic and adrenal beds, with skeletal muscle accounting for about 44% and the kidneys accounting for about 18% of dopa in arterial plasma. Whereas chemical sympathectomy decreased the femoral and renal spillover of dopa by 90% or more, arterial dopa levels and estimated dopa spillover into arterial plasma were decreased by only about 45%. 5. The kidneys accounted for 22% of dopa clearance from arterial plasma. From the renal extraction of I-[3H]dopa and the urinary excretion of [3H]dopamine, it was estimated that 77% of dopa removed in the kidneys was excreted as dopamine in intact animals and 69% was excreted as dopamine in sympathectomized animals. Conversely, about 80% of urinary endogenous dopamine was derived from plasma dopa, regardless of 6-hydroxydopamine treatment. 6. The results indicate that endogenous dopa in arterial plasma is derived substantially but not exclusively from sympathetic nerve endings that are destroyed by 6-hydroxydopamine, especially in skeletal muscle and the kidneys. Regional dopa spillover therefore probably reflects regional catecholamine biosynthesis. In rats, urinary dopamine is derived mainly from renal decarboxylation of circulating dopa.
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44

Morosanova, Maria A., Tatyana V. Fedorova, Alexandra S. Polyakova, and Elena I. Morosanova. "Agaricus bisporus Crude Extract: Characterization and Analytical Application." Molecules 25, no. 24 (December 18, 2020): 5996. http://dx.doi.org/10.3390/molecules25245996.

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In the present work crude Agaricus bisporus extract (ABE) has been prepared and characterized by its tyrosinase activity, protein composition and substrate specificity. The presence of mushroom tyrosinase (PPO3) in ABE has been confirmed using two-dimensional electrophoresis, followed by MALDI TOF/TOF MS-based analysis. GH27 alpha-glucosidases, GH47 alpha-mannosidases, GH20 hexosaminidases, and alkaline phosphatases have been also detected in ABE. ABE substrate specificity has been studied using 19 phenolic compounds: polyphenols (catechol, gallic, caffeic, chlorogenic, and ferulic acids, quercetin, rutin, dihydroquercetin, l-dihydroxyphenylalanine, resorcinol, propyl gallate) and monophenols (l-tyrosine, phenol, p-nitrophenol, o-nitrophenol, guaiacol, o-cresol, m-cresol, p-cresol). The comparison of ABE substrate specificity and affinity to the corresponding parameters of purified A. bisporus tyrosinase has revealed no major differences. The conditions for spectrophotometric determination have been chosen and the analytical procedures for determination of 1.4 × 10−4–1.0 × 10−3 M l-tyrosine, 3.1 × 10−6–1.0 × 10−4 M phenol, 5.4 × 10−5–1.0 × 10−3 M catechol, 8.5 × 10−5–1.0 × 10−3 M caffeic acid, 1.5 × 10−4–7.5 × 10−4 M chlorogenic acid, 6.8 × 10−5–1.0 × 10−3 M l-DOPA have been proposed. The procedures have been applied for the determination of l-tyrosine in food supplements, l-DOPA in synthetic serum, and phenol in waste water from the food manufacturing plant. Thus, we have demonstrated the possibility of using ABE as a substitute for tyrosinase in such analytical applications, as food supplements, medical and environmental analysis.
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45

Baines, A. D., P. Ho, and R. Drangova. "Proximal tubular dopamine production regulates basolateral Na-K-ATPase." American Journal of Physiology-Renal Physiology 262, no. 4 (April 1, 1992): F566—F571. http://dx.doi.org/10.1152/ajprenal.1992.262.4.f566.

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Regulation of proximal tubular Na-K-adenosine-triphosphatase (ATPase), brush-border membrane Na(+)-H+ antiporter and Na(+)-Pi symporter activity by endogenously produced dopamine was examined in Wistar rats. Na-K-ATPase was measured in basolateral membrane (BLM) fractions permeabilized with alamethicin or sodium dodecyl sulfate (SDS). Carbidopa (5 mg/kg) injected 18 h before removal of kidneys increased maximal activity (Vmax) noncompetitively in cortical BLM but not in other membrane fractions or outer medullary BLM (-2 +/- 4%). Chronic renal denervation did not alter the response. Carbidopa stimulated Na-K-ATPase in cortical BLM from rats eating a normal salt diet with and without 1% saline to drink (+18 +/- 4% and +22 +/- 4%, respectively; P greater than 0.001). Carbidopa did not increase Vmax of BLM Na-K-ATPase from rats eating a low-salt diet (+1.5 +/- 4%); however, when the low-salt diet was supplemented with 1 mM dihydroxyphenylalanine (dopa) to drink for 1 day carbidopa, increased Vmax by 18 +/- 3% (P = 0.018). Carbidopa did not alter the Michaelis constant (Km) for Na or K or inhibitory constant (Ki) for ouabain. Injection of the DA1 antagonist Sch 23390 (2 mg/kg) also increased Na-K-ATPase (18 +/- 4%; P = 0.014). Western blots using a monoclonal alpha-subunit antibody revealed a 22 +/- 8% increase following carbidopa treatment (P = 0.033; n = 19 pairs). Carbidopa had no effect on Na(+)-H+ antiporter activity (22Na uptake) or on Na(+)-32Pi cotransport in brush-border membrane vesicles. These results indicate that dopamine produced in proximal tubules tonically reduces Na-K-ATPase Vmax by decreasing the number of alpha-subunits associated with the BLM.
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46

Nicoletti, Ferdinando, Ingrid Philippens, Paolo Fagone, Clarence N. Ahlem, Christopher L. Reading, James M. Frincke, and Dominick L. Auci. "17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) Is Neuroprotective and Reduces Motor Impairment and Neuroinflammation in a Murine MPTP Model of Parkinson’s Disease." Parkinson's Disease 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/969418.

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17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson’s disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2 sec versus 90.9 sec,P<0.0001), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%,P=0.002; tumor necrosis factorα, 40%,P=0.038, and interleukin-1β, 33%,P=0.02) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle (P=0.003), and decreased the numbers of damaged neurons by 38% relative to vehicle (P=0.029). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation.
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47

Esler, M. D., A. G. Turner, D. M. Kaye, J. M. Thompson, B. A. Kingwell, M. Morris, G. W. Lambert, G. L. Jennings, H. S. Cox, and D. R. Seals. "Aging effects on human sympathetic neuronal function." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 268, no. 1 (January 1, 1995): R278—R285. http://dx.doi.org/10.1152/ajpregu.1995.268.1.r278.

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To study the effect of aging on human sympathetic nervous function, we applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20-30 yr) and older (aged 60-75 yr) healthy men. Mean plasma norepinephrine concentration was 66% higher in older men, attributable to 22% lower norepinephrine plasma clearance (P < 0.05) and 29% higher norepinephrine spillover to plasma (difference not statistically significant). Regional venous sampling disclosed that sympathetic outflow to all organs was not activated by aging. Renal norepinephrine spillover was normal in older men. Although spillover of norepinephrine from the heart was increased in older men, 21.1 +/- 11.4 ng/min compared with 11.4 +/- 8.6 ng/min (P < 0.05), diminished norepinephrine reuptake rather than increased cardiac sympathetic nerve firing was the most likely cause, although somewhat reduced intracardiac methylation of norepinephrine with aging also possibly contributed. The extraction of tritiated norepinephrine from plasma during transit through the heart was reduced, suggesting neuronal norepinephrine reuptake was lowered and overflow of the norepinephrine precursor dihydroxyphenylalanine and metabolites dihydroxyphenylglycol and 3-methoxy-4-hydroxy phenylglycol was normal, indicating that norepinephrine synthesis and release were not increased.
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48

Eldrup, Ebbe, Svend Erik Møller, JAN Andreasen, and Niels Juel Christensen. "Effects of Ordinary Meals on Plasma Concentrations of 3,4-Dihydroxyphenylalanine, Dopamine Sulphate and 3,4-Dihydroxyphenylacetic Acid." Clinical Science 92, no. 4 (April 1, 1997): 423–30. http://dx.doi.org/10.1042/cs0920423.

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1. Plasma concentrations of 3,4-dihydroxyphenylalanine (DOPA), dopamine sulphate (DA-S), and 3,4-dihydroxyphenylacetic acid (DOPAC) in humans have been claimed to be indexes of sympathetic nervous activity, but the source and significance of plasma DOPA, DOPAC and DA-S have not been completely elucidated. 2. The effects of ordinary meals on plasma concentrations of total dopamine, mainly DA-S, DOPAC and DOPA were studied in seven healthy subjects. Venous blood was collected every hour for 25 h, while subjects were either fasting or received three meals at 9.00 hours, 13.00 hours and 18.00 hours. Catecholamines and metabolites were determined by reverse-phase HPLC with electrochemical detection. Neutral amino acids were measured by ionexchange chromatography with photometric detection. 3. The food contained relatively little DOPA as compared with phenylalanine, tyrosine, isoleucine and tryptophan. The content of DA and DA-S varied considerably, with the greatest amount in the evening meal of open sandwiches. 4. Plasma DOPA decreased significantly after the meals at 13.00 hours and 18.00 hours, whereas concentrations of the other amino acids increased as expected. 5. Plasma DA-S increased significantly after meals and especially after the evening meal. Increments in DA-S above basal values after a meal were closely related to the content of DOPA+DA+DA-S in the meal. Plasma DOPAC increased significantly after the evening meal. 6. The decrease in plasma DOPA observed after a meal was probably due to uptake of DOPA by muscle tissue. Changes in plasma DA-S and DOPAC during this 25-h study reflected to a large extent the content of DOPA, DA and DA-S in the meals.
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49

Foster, Steven B., Monika Z. Wrona, Jilin Han, and Glenn Dryhurst. "The Parkinsonian Neurotoxin 1-Methyl-4-Phenylpyridinium (MPP+) Mediates Release ofl-3,4-Dihydroxyphenylalanine (l-DOPA) and Inhibition ofl-DOPA Decarboxylase in the Rat Striatum: A Microdialysis Study." Chemical Research in Toxicology 16, no. 10 (October 2003): 1372–84. http://dx.doi.org/10.1021/tx030015l.

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50

Rosenblad, Carl, Qin Li, Elsa Y. Pioli, Sandra Dovero, André SLM Antunes, Leticia Agúndez, Martino Bardelli, et al. "Vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson’s disease." Brain 142, no. 8 (June 26, 2019): 2402–16. http://dx.doi.org/10.1093/brain/awz176.

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Abstract Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson’s disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson’s disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5’-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson’s disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.
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