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)

Post-mortem brain material from control and Parkinson's disease patients was examined to elucidate further the neurochemistry of this disease and to determine the mechanism of action of L-dopa as a therapeutic agent. The activities of L-aromatic amino acid decarboxylase (dopa D), tyrosine hydroxylase, monoamine oxidase and catechol-O-methyl transferase were examined; in addition the tissue levels of dopa, 3-O-methyldopa, dopamine (DA) and homovanillic acid (HVA) were determined. In the non-dopa-treated Parkinsonian patients, the greatest decreases were detected for striatal DA and dopa D, with homovanillic acid and tyrosine hydroxylase levels showing a lesser change. The activities of monoamine oxidase and catechol-O-methyl transferase in the striatal nuclei were not different from the controls. The putamen was consistently the most severely affected region. Dopa and 3-O-methyldopa were detectable in all brain areas only in those patients treated with L-dopa shortly before death. The mean concentrations of DA in the striatum of these patients were 1) 9 to 15 times higher than those in non-dopa-treated patients, 2) related to the time before death of the last dose of L-dopa and 3) greater in the striatum of patients clinically classified as "good responders" as compared to "poor responders." Although L-dopa therapy increased homovanillic acid levels in all brain areas, a preferential increase was observed in the striatum. It was concluded that L-dopa's principal therapeutic effects in Parkinson's disease are consistent with its transformation to DA in the striatum.
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PMID:The neurochemistry of Parkinson's disease: effect of L-dopa therapy. 0 Apr 89

These experiments were designed to study the mechanism of depletion of dopamine (DA) in the striatum produced by alpha-methyl-m-tyrosine (alpha-MMT). alpha-Methyl-m-tyramine (alpha-MMTA), the metabolite of alpha-MMT, appears to be the active DA-depleting agent, since the administration of a decarboxylase inhibitor before alpha-MMT markedly reduced both the formation of alpha-MMTA and the depletion of DA. After injection of alpha-MMT (100 mg/kg i.p.), the striatal concentration of homovanillic acid (HVA) rose by 41% at 1 hour. This is probably due to an increase in DA metabolism, since alpha-MMT markedly enhanced the decline of DA produced by alpha-methyl-p-tyrosine (alpha-MPT). At 2, 3 and 4 hours after alpha-MMT, the concentration of HVA and dihydroxyphenylacetic acid was below control level. The decrease in dihydroxyphenylacetic acid is due partially to a decreased formation of dihydroxyphenylacetic acid from DA. In striatal slices, both alpha-MMT and alpha-MMTA decreased the formation of 3H-H2O and the accumulation of 3H-DA from 1-3,5-3H-tyrosine. Alpha-MMT did not alter the specific activity of 3H-tyrosine or release 3H-DA from the slices, but it did inhibit the activity of tyrosine hydroxylase in striatal homogenates at low concentrations of tyrosine (10 muM). Alpha-MMTA released both newly synthesized and exogenously accumulated 3H-DA from striatal slices. At low concentrations of alpha-MMTA, the percent reduction in 3H-H2O was much greater than the percentage of 3H-DA released into the medium. However, at higher concentrations, the inhibition of 3H-H2O reached a maximum while 3H-DA release kept increasing. These results suggest that both inhibition of tyrosine hydroxylase activity and DA release from storage sites by alpha-MMTA may account for the depletion of DA produced by the injection of alpha-MMT.
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PMID:Studies on the mechanism of depletion of striatal dopamine by alpha-methyl-m-tyrosine. 0 Apr 90

Gamma-hydroxybutyric acid (GHBA) in doses that increased the striatal dopamine (DA) content of rat brain failed to increase the affinity of striatal tyrosine hydroxylase (TH) for its pterdine cofactor or to change the sensitivity of the enzyme to the inhibition by DA. Haloperidol (1 mg/kg) decreased the apparent Km of striatal TH for the pteridine cofactor. However, when GHBA was injected before haloperidol it prevented the decrease in the apparent Kn of TH, in a dose related manner. In vitro GHBA (10(-4) M) neither changed the stimulation of the striatal adenylyl cyclase by DA nor its inhibition by haloperidol. These results suggest that in striatal dopaminergic terminals the Kn of TH for the pteridine cofactor is regulated by an molecuular mechanism which requires that the impulse flow in the DA neurons is unimpaired.
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PMID:The regulation of striatal tyrosine hydroxylase. Effects of gamma hydroxybutric acid and healperidol. 0 Jun 29

A single exposure to a severe stressor (either cold swim or inescapable shock) impairs subsequent performance in a shuttle avoidance-escape task (1), a deficit attributed to reduction in brain noradrenergic activity produced by these stressors. In the present paper, two experiments are described which examine how repeated exposure to such stressors affects (a) shuttle avoidance-escape performance (Experiment 1), and (b) aspects of brain norepinephrine metabolism (Experiment 2). Experiment 1 showed that, whereas subjects receiving the single exposure to cold swim or shock showed a large avoidance-escape deficit, subjects that received repeated exposure to these stressors for 14 days performed similarly to the control group that received no stressor. Experiment 2 showed that, whereas subjects that received one session of the inescapable shock stressor showed a lower level of norepinephrine in hypothalamus and cortex than did subjects that received no shock, subjects that received repeated exposure to inescapable shock or cold swim showed neurochemical "habituation." Subjects that received repeated shock showed elevated tyrosine hydroxylase activity and no depletion of norepinephrine level, and both repeated shock and cold swim caused a decrease in uptake of 3H-norepinephrine by slices of cortex in vitro. Thus, it is concluded that the behavioral and neurochemical changes that were observed after the stressful conditions studied are consistent with the hypothesis that changes in avoidance-escape responding following exposure to these stressful events are due to changes in brain noradrenergic activity.
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PMID:Effects of chronic exposure to stressors on avoidance-escape behavior and on brain norepinephrine. 0 Jul 11

In the albino rat, the evolvement of myocardial necrosis induced by a single injection of ISO was accompanied by a fall in total NE. Pretreatment with propranolol and pargyline protected against ISO-induced necrosis and myocardial hypertrophy, but did not influence the ISO-induced depletion of NE stores. The depletion of NE stores is not due to impairment in synthesis or increased intraneuronal metabolism of NE since, in ISO-treated rats, neither cardiac tyrosine hydroxylase activity nor MAO activity was altered. The decrease in endogenous NE is not due to a defect in the storage of NE. The ability of myocardium to take up and store NE returned to normal within 48 hours, whereas endogenous levels returned to normal within 5 days, even in the presence of demonstrable necrosis. Thus, there is lack of correlation between chemical and morphological changes, since catecholamine depletion occurred in the absence of morphologically demonstrable tissue injury, and the function of the adrenergic neuron returns to normal in the presence of demonstrable necrosis.
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PMID:Alterations in norepinephrine pattern in the damaged myocardium in the rat. 0 Jul 42

A transplantable mouse testicular teratoma (OTT 6050) which displays a spectrum of neuroepithelial differentiation was evaluated biochemically for concentrations of cyclic AMP (cAMP), serotonin (5-HT), and enzymes involved in the metabolism of the biogenic amines and acetylcholine. These values were compared between teratomas with neuroepithelial differentiation as the major or minor component and brains of neonatal and adult mice of related strains. cAMP, 5-HT, tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were present. In addition, enzymes of the adrenergic system, i.e. tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and of the cholinergic system, i.e. choline acetyltransferase and acetylcholinesterase, were studied. Biochemical differences in tumor groups probably reflected variations in the proportion of neuroepithelial components: trends suggested an increase of cAMP and an increased activity of TPH, AADC, TH and DBH in tumors with increased proportions of neuroepithelial cells. These findings indicate that the neuroepithelial component of the mouse teratoma may serve as a model for the study of neuronal differentiation in primitive neuroepithelial neoplasms.
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PMID:Neurochemical studies in a mouse teratoma with neuroepithelial differentiation. Presence of cyclic AMP, serotonin and enzymes of the serotonergic, adrenergic and cholinergic systems. 0 Nov 40

To examine the regulation of development of end organ innervation the superior cervical ganglion (SCG), and two of its target organs, the iris and pineal gland, were studied using biochemical and histofluorescent approaches. During postnatal ontogeny the activity of tyrosine hydroxylase (T-OH), which is localized to adrenergic neurons, increased 50-fold in iris, and 34-fold in pineal nerve terminals of the rat. These increases paralleled the in vitro rise in iris [3H]norepinephrine ([3H]NE) uptake, a measure of the presence of functional nerve terminal membrane. These biochemical indices of end organ innervation correlated well with developmental increases in density of innervation, adrenergic ground plexus ramification and nerve fiber fluorescence intensity as determined by fluorescence microscopy. Unilateral transection of the presynaptic cholinergic nerves innervating the SCG in 2-3-day-old rats prevented the normal development of end organ innervation: T-OH activity, [3H]NE uptake, innervation density, plexus ramification and fluorescence intensity failed to develop normally in irides innervated by decentralized ganglia. It is concluded that trans-synaptic factors regulate the maturation of adrenergic nerve terminals, and the development of end organ innervation by SCG.
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PMID:Trans-synaptic regulation of the development of end organ innervation by sympathetic neurons. 0 Nov 41

The administration of guanethidine to adult rats has been shown by morphological criteria to destroy sympathetic neurons. The objective of this study was to evaluate by biochemical and functional criteria the degree and permanence of this sympathectomy. Young adult male rats (260-300 g) were injected with saline (controls) or with guanethidine for 5 weeks. The status of the sympathetic nervous system in the animals was evaluated 1, 3 and 6 to 7 months after cessation of treatment. Seven months after cessation of treatment; the activity of tyrosine hydroxylase in the superior cervical ganglia of treated animals was greatly reduced, as were the norepinephrine levels in peripheral tissues. The concentration of epinephrine and the activity of tyrosine hydroxylase in adrenals were not different from controls at any of the times studied. Norepinephrine concentrations in several areas of the central nervous system were unchanged. Increases in blood pressure in response to stimulation of the sympathetic vasomotor outflow in the pithed rat preparation were markedly and permanently reduced in guanethidine-treated animals. Isolated intestinal nerve-muscle preparations from guanethidine-treated animals usually contracted in response to nerve stimulation, rather than relaxing as in controls. The response to stimulation of the hypogastric nerve in vas deferens preparations was reduced 1 month after cessation of treatment. The responses of the vas deferens from guanethidine-treated and control animals were the same 7 months after treatment despite a 93% reduction in norepinephrine concentration. The data demonstrate that the administration of guanethidine to adult rats produces a marked and permanent destruction of the peripheral sympathetic nervous system.
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PMID:Evaluation of the permanent sympathectomy produced by the administration of guanethidine to adult rats. 0 17

Clonal mouse neuroblastoma cells without tyrosine 3-monooxygenase [EC 1.14.16.2; tyrosine hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] activity were fused with normal cells from embryonic mouse sympathetic ganglia. One of the 37 hybrid cell lines obtained possesses high tyrosine 3-monooxygenase activity and synthesizes dopamine. These cells also have excitable membranes and generate action potentials in response to electrical stimuli. Thus hybrid cells, generated by fusion of neuroblastoma cells with normal cells from the nervous system, can acquire neural properties not found with the parental neuroblastoma cells.
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PMID:Neuronal properties of hybrid neuroblastoma X sympathetic ganglion cells. 0 45

Addition of dimethylsulfoxide at concentrations of 1% and 2% (vol/vol) to cells of mouse neuroblastoma clone NIE-115 in the confluent phase of growth resulted in the production of morphologically differentiated cultures with extensive process formation. Cell maintained in 2% dimethylsulfoxide remained in a stable nondividing condition for periods of up to 4 weeks. A high degree of electrical excitability was found in these cells, but there was no clear correlation of this property with the level of induction of either acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) or tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2]. In addition, intracellular levels of cyclic 3':5'-AMP were not elevated in fully morphologically and electrically differentiated cells. While cell division was markedly inhibited by 2% or higher concentrations of dimethylsulfoxide, at 1% growth continued at a somewhat slowed rate and such cultures exhibited enhanced process formation and electrical activity for a relatively short period. High concentrations (3% or 4%) of dimethylsulfoxide totally suppressed process formation and did not result in increased excitability, but cells maintained high resting potentials. The results suggest that the development of the excitable membrane in neuroblastoma cells may be expressed independently of neurospecific enzyme induction, and does not require a sustained elevation of cyclic 3':5'-AMP levels.
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PMID:Maturation of neuroblastoma cells in the presence of dimethylsulfoxide. 0 56


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