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

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

Clinical reports indicate that cessation of treatment with the antihypertensive agent clonidine is associated with a withdrawal syndrome which may include a hypertensive overshoot of critical proportions. We have attempted to produce an animal model of this syndrome in rats. Rats were treated with clonidine in the drinking water (5 microgram/ml; total dose 300-500 microgram/kg/day) which produced a significant (approx. 20%) decrease in heart rate and blood pressure. Within 24 h of cessation of treatment a significantly greater (approximately 100 beats/min) heart rate was seen in treated animals than in control animals when measurements were made in conscious animals. No hypertensive overshoot was observed. Cessation of treatment was associated with an increase in sympatho-adrenal tone as shown by a trans-synaptic induction of adrenal tyrosine hydroxylase activity. Adrenal denervation prevented the rise in adrenal tyrosine hydroxylase seen after cessation of treatment. Administration of clonidine to pregnant rats (10th day until term) did not alter the development of adrenal tyrosine hydroxylase in the offspring. The data indicate that a withdrawal syndrome is produced upon cessation of chronic clonidine treatment.
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PMID:Withdrawal syndrome upon cessation of chronic clonidine treatment in rats. 1 57

Validity of the tritiated water assay technique for tyrosine hydroxylase activity as a qualitative method was demonstrated with mushroom tyrosinase. Using this method, isolated murine melanoma "tyrosinase" (L-dopa oxidase) showed no tyrosine hydroxylase activity. This finding supports previous studies in our laboratory which used a variety of histochemical and biochemical methods. The nonenzymatic production of tritiated water caused by tritium exchange with hydrogen peroxide complicates the use of the tritiated water assay technique with crude systems, since hydrogen peroxide is generated by a variety of oxidase reactions. For this reason, previous studies using the tritiated water assay technique with crude systems are ambiguous.
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PMID:Inability to demonstrate hydroxylation of tyrosine by murine melanoma "tyrosinase" (L-DOPA oxidase), using the tritiated water assay technique. 10 47

The effect of alpha-methyldopa and alpha-methyldopamine (alpha-MDA) on the rate of hydroxylation of radioactive tyrosine was studied in striatal slices from rat brain. This was done by measuring the formation of 3-H-H2O as well as the accumulation of 3-H-dopamine (3-H-DA) from L-3, 5-3-H-tyrosine. alpha-Methyldopa, at tissue concentrations similar to those found in vivo after systemic administration, produced a decrease in both 3-H-H2O and 3-H-DA. The marked decrease (91thyldopa injection, also inhibited 3-H-H2O formation. The inhibitory effect of alpha-methyldopa on 3-H-H2O formation was not reduced by the addition of brocresine, which prevents the formation of alpha-MDA. The effects of alpha-methyldopa and alpha-MDA on the release of 3-H-DA that had been taken up into brain slices, was also studied. Although alpha-methyldopa, 1000 muM, did not increase the release of 3H-DA from tissue, alpha-MDA did. However, the latter was more potent in inhibiting 3-H-H2O formation from 3-H-tyrosine than in releasing 3-H-DA. These results, as well as the close similarity between the percent reduction of 3-H-H2O formation and tissue 3-H-DA levels, suggest that alpha-methyldopa decreases tissue levels of dopamine by inhibiting tyrosine hydroxylase activity in DA neurons.
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PMID:Effect of alpha-methyldopa on dopamine synthesis and release in rat striatum in vitro. 23 16

The response of six mRNAs (for prepro-corticotropin-releasing hormone, prepro-enkephalin, prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, prepro-neurotensin/neuromedin N, prepro-cholecystokinin, and prepro-tyrosine hydroxylase) was measured in the hypothalamic paraventricular and supraoptic nuclei after increasing periods of osmotic stimulation caused by the replacement of regular drinking water with hypertonic saline (up to five days) or by forced dehydration (up to three days). In addition, hematocrits and concentrations of corticosterone were determined after the different periods of osmotic stimulation and correlated with the effects on the content of the various mRNAs. The temporal response of the mRNAs within the paraventricular and supraoptic nuclei to osmotic stimulation was different within the three compartments of these nuclei. First, in response to overnight osmotic stimulation, magnocellular neurosecretory neurons increased their mRNA content for two molecules (prepro-corticotropin-releasing hormone and tyrosine hydroxylase). As the stimulus was maintained over the next two to four days, these cells accumulated the mRNAs for at least three other peptides (cholecystokinin, vasoactive intestinal polypeptide/peptide histidine isoleucine and enkephalin). Second, the response of peptide-coding mRNAs in parvicellular neurosecretory neurons of the paraventricular nucleus appeared to be slower; no changes could be measured after overnight stimulation. However, after a further two- to four-days of continued osmotic stimulation, the content of the mRNA coding for corticotropin-releasing hormone markedly decreased while that for cholecystokinin increased. No change in the content of the mRNAs coding for prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, enkephalin, and prepro-neurotensin/neuromedin N could be seen at any time after osmotic stimulation in parvicellular neurosecretory neurons. Third, increases in the content of mRNA coding for corticotropin-releasing hormone in the parvicellular neurons that provide descending projections from the paraventricular nucleus could only be detected after longer periods of osmotic stimulation. The effect of osmotic stimulation on plasma corticosterone concentrations was quickly apparent; plasma corticosterone concentrations were significantly elevated on the first morning after the beginning of salt-loading, and demonstrated the rapid effects of osmotic stimulation on the mechanisms controlling corticosterone release. These results show that the synthetic capability of cells in all three compartments of the paraventricular and supraoptic nuclei are modified by osmotic stimulation over different time scales, thereby allowing differential modulation of the neuroendocrine, autonomic, and behavioral components of the animal's response to disturbances in fluid homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Disturbance of fluid homeostasis leads to temporally and anatomically distinct responses in neuropeptide and tyrosine hydroxylase mRNA levels in the paraventricular and supraoptic nuclei of the rat. 134 11

The effects of aging and chronic ethanol administration on the histochemical and morphometric features of rat superior cervical ganglion were studied in a rat strain selected for voluntary alcohol consumption. Ethanol was administered to the experimental group ad libitum (10% v/v in drinking water) from 3 months to 28 months of age, the average ethanol intake being 6.4-5.4 g/kg per day. The sympathetic neurons of the ethanol consuming rats showed several signs of enhanced degeneration, e.g. decreased neuronal packing density, increased amount of age-pigment and decreased intensity of catecholamine histofluorescence and tyrosine hydroxylase immunoreactivity. The results may indicate a selective vulnerability of peripheral sympathetic neurons rather than a universal accelerated aging due to chronic ethanol exposure.
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PMID:Lifelong ethanol consumption enhances the age-related changes in rat sympathetic neurons. 135 Nov 24

Norepinephrine (NE) content, release and uptake by brain synaptosomes are reduced in chronic renal failure (CRF), and this has been attributed to the state of secondary hyperparathyroidism. The decrease in NE content in CRF could not be explained by changes in NE uptake or release since in normal circumstances, NE content usually remains unchanged despite fluctuation in NE uptake and release. Since NE content is determined by its production and degradation, we examined the effect of CRF with and without excess parathyroid hormone (PTH) on the Michaelis-Menton constant (Km) and Vmax of tyrosine hydroxylase (TH), the rate-limiting enzyme for NE production, and monoamine oxidase (MAO), an enzyme involved in NE degradation of brain synaptosomes. Brain synaptosomes from rats with a 21-day CRF have a significantly (p less than 0.01) lower Vmax of TH (39.5 +/- 5.3 pmol tritiated H2O/mg protein/min) than that of normal rats (61. +/- 7.5 pmol tritiated H2O/mg protein/min) and a higher Km of MAO (59 +/- 2.9 nM tyramine) than normal animals (46 +/- 1.7 nM tyramine). Parathyroidectomy (PTX) in CRF rats normalized Vmax of TH (54 +/- 4.5 pmol tritiated H2O/mg protein) and Km of MAO (48.4 +/- 2.3 nM tyramine). Cytosolic calcium, [Ca2+]i, in brain synaptosomes is significantly (p less than 0.01) higher in rats with CRF (488 +/- 8.5 nM) than in normal (355 +/- 6.0 nM) or PTX-CRF (360 +/- 8.1 nM) rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of chronic renal failure with and without secondary hyperparathyroidism on the activities of synaptosomal tyrosine hydroxylase and monoamine oxidase. 135 40

Previous work has indicated that the neurotoxic action of environmentally relevant levels of lead (Pb) on dopaminergic neurons is primarily presynaptic in nature and related to impaired regulation of dopamine (DA) synthesis and decreased DA release. This study was conducted to assess the functional integrity of the regulation of DA synthesis in caudate-putamen (C-P) and nucleus accumbens (NAc) of chronically Pb-exposed rats by measuring tyrosine hydroxylase (TH) activity. A pharmacological paradigm was employed that isolated autoreceptor-mediated regulation of the enzyme. At parturition dams received 0.2% Pb acetate (1090 ppm) in the drinking water while control dams received distilled water. Offspring were weaned to and maintained on the same solution given their dams until termination at 60 or 120 days. Rats were given saline or one of three DA agonists (EMD 23448, CGS 15855A, TL-99) 45 or 60 min before termination followed 15 min later by 750 mg/kg i.p. of gamma-butyrolactone (GBL) or saline. The ability of a DA agonist to prevent the GBL-induced increase in DA content was significantly altered in C-P of exposed rats compared to controls. No effect of Pb on DA content was observed in NAc. Furthermore, no differences in the ability of DA agonists to inhibit GBL-induced activation of TH in Pb-exposed compared to control animals were apparent in either brain region at either age by use of the tritium release method or the accumulation of L-DOPA. On the other hand, concentrations of DA metabolites in exposed rats given GBL and EMD 23448 were significantly lower than those in controls in both C-P and NAc. These findings support previous work suggesting that chronic Pb has multiple actions on CNS dopaminergic neurons consisting of impaired regulation of DA content and decreased DA release. However, these effects cannot be attributed to alterations in autoreceptor-mediated regulation of TH activity.
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PMID:Regulation of dopaminergic activity, but not tyrosine hydroxylase, is diminished after chronic inorganic lead exposure. 136 80

The effect of copper on the concentrations of o- and m-tyrosines in the serum of guinea pigs was studied in vivo. When guinea pigs were fed the normal diet and 0.1% CuSO4 solution as a drinking water for 13 d, the concentrations of o- and m-tyrosines in the serum increased more significantly than that of guinea pigs fed normal diet and water without copper. Phenylalanine hydroxylase in the liver and kidney, and tyrosine hydroxylase in the brain and adrenal were not activated by the administration of copper to guinea pigs. The administration of copper caused an abnormal accumulation of copper in the liver, but not in the kidney, adrenal and brain, and significantly depressed the ascorbic acid content in various organs including the liver, kidney, brain and adrenal. The results obtained suggest that o- and m-tyrosines may be also formed nonenzymatically in vivo, in addition to the formation by the participation of enzymes such as phenylalanine and tyrosine hydroxylases.
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PMID:[The effect of copper on o- and m-tyrosine content in the serum of guinea pigs]. 168 10

In situ hybridization histochemistry and indirect immunofluorescence histochemistry were used to study changes in the expression of vasopressin (VP), oxytocin (OXY), tyrosine hydroxylase (TH), galanin (GAL), dynorphin (DYN) and cholecystokinin (CCK) in hypothalamic magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei of rats. After prolonged administration of 2% sodium chloride as drinking water (salt-loading), the treatment increased the levels of VP, OXY, TH, GAL, DYN and CCK mRNA in the PVN and SON. The increase in CCK mRNA was, however, proportionally higher in the PVN than in the SON. Within cell bodies of the PVN and SON of salt-loaded rats, a depletion of VP- and OXY-like immunoreactivity (LI) and an increase in TH-LI were seen. In salt-loaded/colchicine-treated rats, a marked decrease in GAL- and DYN-LI, but no specific changes in CCK-LI were observed. Within nerve fibers of the posterior pituitary of salt-loaded rats, a marked depletion of VP-, GAL- and DYN-LI was found. Less pronounced depletion was observed in OXY- and CCK-LI, and no specific changes in TH-LI were seen. The results show that high plasma osmolality induces increased mRNA levels for VP, OXY, TH, GAL, DYN and CCK, presumably indicating increased synthesis, an increased export from cell somata of VP, OXY, GAL and DYN, and a decrease in levels of these peptides in the posterior pituitary, suggesting increased release. The catecholamine-synthesizing enzyme TH, however, which has a cytoplasmic localization and is not released from nerve endings, remains high in the cell bodies and nerve endings during this state of increased activity.
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PMID:Peptides and transmitter enzymes in hypothalamic magnocellular neurons after administration of hyperosmotic stimuli: comparison between messenger RNA and peptide/protein levels. 169 5


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