Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Earlier reports from this and other laboratories have indicated that wide variations exist in estimates of the concentrations of norepinephrine in the brain and heart of the snail Helix aspersa. This is a report on investigations of norepinephrine concentrations in Helix aspersa tissues using high-performance liquid chromatography with electrochemical detection. In addition, the effects of treatment with some amino acid precursors or enzyme inhibitors on the concentrations of norepinephrine, dopamine, 5-hydroxytryptamine, and some of their metabolites were investigated. 2. The levels of norepinephrine in the brain were low (46 ng/g) in comparison to dopamine (2.1) micrograms/g) and 5-hydroxytryptamine (2.6 micrograms/g). Epinephrine was not observed in either snail heart of snail nervous tissue. 3. Administration of L-3,4-dihydroxyphenylalanine resulted in elevated snail brain dopamine, while 3,4-dihydroxyphenylserine treatment increased norepinephrine. Treatment with blockers of tyrosine hydroxylase and aromatic-L-amino acid decarboxylase reduced dopamine concentrations without affecting 5-hydroxytryptamine. 4. The dopamine metabolite 3,4-dihydroxyphenylacetic acid was observed only after administration of L-3,4-dihydroxyphenylalanine or dopamine and then only in very small amounts. At no time was the dopamine metabolite homovanillic acid or the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid observed in brain, heart, or whole-body extracts of the snail. 5. Incubation of nervous tissue with either dopamine or 5-hydroxytryptamine resulted in the production of electrochemically active metabolites which were identified by oxidation characteristics and cochromatography with synthesized standards as the gamma-glutamyl conjugates of the amines. Treatment of snails with 5-hydroxytryptamine or dopamine also resulted in the production of gamma-glutamyl conjugates. 6. The present experiments show that great care must be exercised when measuring monoamines and their metabolites in gastropod tissues by high-performance liquid chromatography with electrochemical detection.
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PMID:High-performance liquid chromatographic analysis of monoamines and some of their gamma-glutamyl conjugates produced by the brain and other tissues of Helix aspersa (Gastropoda). 211 17

I studied the neuropsychiatric disorders occurring after overdose with manganese (Mn), which have been shown to be neurologically similar to Parkinson's disease. MnCl2 doses of 10 mg Mn/kg, administered a total of 15 times, were injected intraperitoneally into rats. Then I determined the concentration of monoamines, their metabolites and the activity of catecholamine-related enzymes of the rat brain using high-performance liquid chromatography (HPLC). 1) In the Mn-loaded rats, the concentration of dopamine (DA) was significantly decreased in the nucleus caudatus-putamen (C/P)(p less than 0.05), the thalamus (p less than 0.05) and in the mesencephalon (ME) (p less than 0.001), while that of homovanillic acid decreased in the C/P (p less than 0.05). The concentration of norepinephrine (NE) was decreased in the hypothalamus (p less than 0.01) and that of 3-methoxy-4-hydroxyphenyl-glycol was decreased in the C/P (p less than 0.001) and in the thalamus (less than 0.05); however serotonin and 5-hydroxyindoleacetic acid concentrations showed no variation from those of the controls. 2) As for the enzymes of catecholamine biosynthesis, tyrosine hydroxylase (TyrOHase) activity was increased in the hypothalamus (p less than 0.05) and was reduced in the ME (p less than 0.01). Dopa decarboxylase activity showed no change. Dopamine-beta-hydroxylase (DBH) activity was reduced in the C/P and the thalamus (p less than 0.05 respectively). Phenylethanolamine-N-methyltransferase activity was detected in the hypothalamus, the ME, and at low levels in the thalamus (p less than 0.01). Among the enzymes of catecholamine metabolism, catechol-O-methyltransferase activity showed no variation, but monoamine oxidase (MAO) type-a and type-a + b activities were significantly increased in the cerebral cortex (p less than 0.01), and MAO type-a + b as significantly reduced in the C/P and the hypothalamus (p less than 0.01). The decrease on DA and NE contents found could be due to the reduction of such biosynthesizing enzymes as TyrOHase and DBH. Especially, the DA content was markedly decreased in the ME, found mostly in regions where DA neurons originate. Thus the variation of this region would be the first disorder. And it was interesting to note that MAO type-a + b was reduced by Mn administration.
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PMID:[Studies on monoamine metabolism in the rat brain with overdosage of manganese]. 240 98

A case of recurrent midgut carcinoid tumour with disseminated spread is described, in which the clinical diagnosis was supported by measurements of elevated basal serotonin (5-HT) levels in peripheral blood and increased 5-HT responses to pentagastrin provocation, despite normal urinary levels of 5-hydroxyindoleacetic acid. Preoperative diagnosis was obtained by concomitant determinations of 5-HT in mesenteric and hepatic veins. The carcinoid tumour was studied immunocytochemically using antisera to tyrosine hydroxylase and 5-HT. Neuroendocrine complexes between adrenergic nerve terminals and 5-HT-containing tumour cells could be demonstrated. 5-HT release from tumour cells in suspension was studied in vitro after incubation with adrenoceptor agonists or pentagastrin. Tissue pieces from the tumour were also transplanted into the anterior eye chamber of Sprague-Dawley rats, some of which were subjected to immunosuppression (Cyclosporin A 20 mg/kg s.c.). After 10 days in oculo the tumour transplants (with preserved immunocytochemical characteristics) were stimulated with adrenoceptor agonists. Tumour cells in suspension as well as tumour transplants released 5-HT upon adrenoceptor stimulation but no release was induced by pentagastrin. The pentagastrin test is suggested to cause release of 5-HT in carcinoid tumour patients via release of endogenous catecholamines, in turn activating adrenoreceptors on carcinoid tumour cells.
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PMID:Adrenergic control of serotonin release from a midgut carcinoid tumour. 241 74

After intraperitoneal injection of rats with 6-fluorotryptophan (6-FT), brain 5-hydroxytryptamine (5-HT) levels decreased exponentially over 1 h. Depletion was dose-dependent and maximum depletion was observed at 200 mg/kg. 6-FT (200 mg/kg) did not significantly alter the content of 5-hydroxyindoleacetic acid. Turnover rates of 5-HT obtained by the 6-FT and other methods were fairly consistent. 6-FT had little effect on the content of noradrenaline and dopamine. These data suggest that 6-FT completely inhibits tryptophan hydroxylase, in vivo, without affecting the release of 5-HT from 5-HT neurons and with little effect on the activities of tyrosine hydroxylase. Therefore, 6-FT is a good pharmacological tool for studying the turnover rate of 5-HT in the brain.
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PMID:Determination of serotonin turnover in the rat brain using 6-fluorotryptophan. 243 50

The kinetics of monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), in cisternal CSF were determined after monoamine oxidase (MAO) inhibition (pargyline, 100 mg/kg) and tyrosine hydroxylase inhibition (alpha-methyl-p-tyrosine, alpha-MPT, 250 mg/kg) in awake rats. In addition, the possibility of a peripheral contribution to CSF MHPG levels was investigated by infusing large amounts of the metabolite into vena jugularis. Pargyline induced an exponential decrease of CSF MHPG, 5-HIAA and HVA, with respective half-lives of 51, 86 and 46 min. alpha-MPT caused a slower decline of MHPG and HVA, while 5-HIAA was unaffected. Results from the MHPG-infusion experiments indicate minor peripheral contribution to CSF MHPG levels in acute pharmacological studies. The present paper gives further support for the validity of our new animal model in detecting acute changes in central monoaminergic activity.
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PMID:Monoamine metabolite levels in rat CSF: kinetic studies. 244 6

The influence of N-ethyl-3,4-methylenedioxyamphetamine (MDE) on the central serotonergic and dopaminergic systems of the rat after a single or multiple injections was studied. MDE (10 mg/kg) produced a significant decrease in the concentration of 5-hydroxytryptamine (5-HT) 1 hr later in the frontal cortex and the hippocampus without affecting the concentration of 5-hydroxyindoleacetic acid (5-HIAA) or tryptophan hydroxylase (TPH) activity. Hypothalamic and neostriatal concentrations of 5-HT, 5-HIAA, dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) remained unaffected, as well as the neostriatal TPH and tyrosine hydroxylase (TH) activities. However, 3 hr after the MDE injection, the serotonergic variables including TPH activity were decreased in most of the brain areas examined. The dopaminergic system remained unaffected, except for a significant reduction in neostriatal DOPAC concentrations. The changes in transmitter concentrations after a single injection were dose dependent; the maximum depletion in TPH activity was reached with a 10 mg/kg dose. The administration of multiple doses of MDE caused greater decreases in TPH activity and 5-HT concentrations 3 hr after the treatment than did a single injection; in addition, a partial recovery from multiple administrations occurred by 18 hr. The effects of MDE on DA and its metabolites were transient, and neostriatal TH activity was not altered. This study demonstrates that MDE primarily affects the central serotonergic system, as reported for its congeners 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine. It does, however, produce less neurotoxicity as judged by its lower potency on the dopaminergic and the serotonergic systems as well as the recovery occurring in these systems.
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PMID:Effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE) on central serotonergic and dopaminergic systems of the rat. 244 29

The response of brain dopaminergic and serotonergic systems to the amphetamine-like designer drugs, 3,4-methylenedioxyamp amphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), was investigated and compared to methamphetamine (METH). Like METH, single or multiple doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) in several brain regions. The reduction in 5HT content corresponded to the depression of TPH activity in all regions examined. In contrast to METH, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin.
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PMID:The effects of amphetamine-like designer drugs on monoaminergic systems in rat brain. 244 19

Young adult male CD-1 mice were treated orally twice weekly for three weeks with 0, 0.05, 0.15 or 0.65 mg/kg of aflatoxin B1 (AFB1) in corn oil. Two days after the last dose, the mice were killed by decapitation and the concentrations of the brain catecholamines, norepinephrine (NE), and dopamine (DA), and their metabolites, 3-methoxy-4-hydroxymandelic (VMA), homovanillic acid (HVA) and dihydroxyphenyl acetic acid (DOPAC) and the indoleamine serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were determined by high pressure liquid chromatography in six discrete brain regions. Major effects of AFB1 were found in the concentrations of NE in most brain areas. Endogenous concentrations of DA were increased in the striatum and hypothalamus. The VMA level in the hypothalamus and striatum were decreased by the treatment. The activity of tyrosine hydroxylase, tryptophan hydroxylase, amino acid decarboxylase and monoamine oxidase (the enzymes important in synthetic and degradation pathways of biogenic amines) were investigated. Alterations in biogenic amine concentrations were often consistent with the changes observed in metabolizing enzymes. There was an increase noted in tryptophan hydroxylase activity. Activities of amino acid decarboxylase and monoamine oxidase were increased although the changes were not consistent in all regions or at all dose levels of AFB1. These results suggest that dietary exposure to AFB1 diets may cause alterations in various biogenic amine concentrations and related metabolizing enzymes.
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PMID:Alteration of biogenic amines in mouse brain regions by alkylating agents. I. Effects of aflatoxin B1 on brain monoamines concentrations and activities of metabolizing enzymes. 249 75

The integrity of forebrain monoamine systems has been assessed both biochemically and immunohistochemically in transgenic mice carrying the mutant hprt-bm2 gene, an animal model of Lesch-Nyhan syndrome. The mutant mice manifested 20-30% depletions of forebrain dopamine, and corresponding increases in dopamine turnover. By contrast, the mutant mice manifested normal tyrosine hydroxylase immunostaining of catecholamine cell bodies and terminals throughout the forebrain, and cell counts revealed no detectable loss of ventral mesencephalic dopamine neurones. Serotonin concentrations were also depleted, whereas no significant changes were found in noradrenaline or adrenaline, methylhydroxyphenylglycol (MHPG) or 5-hydroxyindoleacetic acid. The results indicate that a primary genetic deficiency in purine salvage pathways is associated with additional changes in forebrain monoamine metabolism in mouse as in man, although these changes are less pronounced in the animal model than in the human syndrome. The biochemical changes were not associated with explicit degeneration of the associated populations of neurones.
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PMID:Monoamine deficiency in a transgenic (Hprt-) mouse model of Lesch-Nyhan syndrome. 257 8

Intrastriatal administration of the hydroxylated metabolites of amphetamine, p-hydroxyamphetamine (p-OHA) or p-hydroxy-norephedrine (p-OHNor), decreased local concentrations of dopamine and serotonin in a dose-dependent manner. Although both compounds reduced concentrations of the metabolites of dopamine, 5-hydroxyindoleacetic acid concentrations were elevated. After systemic treatment with p-OHA, striatal dopamine was also reduced. In contrast, only hypothalamic and hippocampal serotonin stores were altered significantly in rats treated with p-OHA systemically. Neither compound decreased the activities of tryptophan hydroxylase or tyrosine hydroxylase. Because p-OHA is metabolized to p-OHNor via dopamine beta-hydroxylase present in noradrenergic neurons, the direct effects of these compounds on dopaminergic and serotonergic variables can be observed in rats which receive intrastriatal drug treatment. p-OHA and p-OHNor were equally potent in decreasing dopamine concentrations. However, p-OHNor was more potent than p-OHA in decreasing serotonin concentrations. Both compounds more readily depleted dopamine compared to serotonin stores. Complete recovery of p-OHA-induced decreases in striatal dopamine occurred within 48 hr of intrastriatal administration and concurrent treatment with the dopamine uptake blocker, amfonelic acid, significantly attenuated the p-OHA-induced effects on dopamine.
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PMID:Neurochemical effects of amphetamine metabolites on central dopaminergic and serotonergic systems. 260 Aug 21


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