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)

6-Hydroxydopamine (6-OH-DA) treatment of rats at birth (with the analyses conducted in the adult stage) produced marked regional variations in changes in endogenous noradrenaline (NA) and [3H]NA uptake in the CNS. The most pronounced reductions were seen in the cerebral cortex, hippocampus and the spinal cord. Moderate changes or none at all were seen in the hypothalamus, septum and thalamus. Marked increases in endogenous NA and [3H]NA uptake were seen in the mesencephalon and the pons-medulla oblongata. There was in general a close correlation between the changes in endogenous NA and [3H]NA uptake. The results from the cerebellum varied, depending on the developmental stage at which the 6-OH-DA treatment was performed. 6-OH-DA treatment up to three days after birth generally led to a marked increase in both endogenous NA and [3H]NA uptake, while continuing the treatment caused a marked reduction of both parameters. The 6-OH-DA treatment caused no changes in endogenous dopamine (DA) in all regions analysed. Enzyme activity assays showed that DA-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) were greatly reduced in the cerebral cortex, while the activity of both enzymes was almost double in the pons-medulla. No changes in the activity of phenylethanol-amine N-methyltransferase (PNMT), DOPA decarboxylase, COMT and MAO were seen after 6-OH-DA at birth. Measurements of choline acetyltransferase activity displayed only minute changes. The present results strongly support the view that 6-OH-DA treatment in the neonate stage produces a very selective action on NA neurones belonging to the locus coeruleus system from a structural standpoint, leaving DA- and PNMT-containing neurones unaffected. [3H]NA uptake in whole CNS was almost unchanged, despite the marked regional variations. The results have been interpreted as being due to a 'pruning effect', where the permanent NA denervation in distant nerve terminal projections (e.g. cerebral cortex) leads to a compensatory sprouting and increased outgrowth of NA terminal projections in areas close to the perikarya (e.g. pons-medulla). Furthermore, the results support the view that the growing locus coeruleus neurones are strictly programmed to produce a certain quantity of nerve terminal volume and arborization during the postnatal development.
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PMID:Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment. 0 70

The audiogenic seizure-inducing drug H13/04 was found to elicit opposing effects on the in vivo accumulation of 5-HTP (5-hydroxytryptophan) and DOPA (3,4-dihydroxyphenylalanine) in the brain following inhibition of L-amino acid decarboxylase. In strains of mice that normally do not exhibit audiogenic seizures, H13/04 retarded the accumulation of 5-HTP in the telencephalon, diencephalon and brainstem and enhanced the accumulation DOPA in the diencephalon and brainstem. The duration of the biochemical action of H13/04-correlated with the duration of the behavioral effect. When H13/04 is administered to strains of mice with a genetically-determined susceptibility to audiogenic seizures, but at an age when they are developing resistance to seizures, H13/04 does not alter the incidence of sound-induced seizures. The effect on the accumulation of 5-HTP and DOPA was similar to that noted in the genetically-resistant strain; a retardation of the accumulation of 5-HTP in the telencephalon and brainstem and an enhancement of DOPA accumulation in the brainstem. Since the rate of accumulation of 5-HTP and DOPA is a measure of the in vivo rates of tryptophan and tyrosine hydroxylase, respectively, the results may reflect changes in neural activity with consequent effects on the synthesizing enzymes. These results emphasize the usefulness of the drug in analyzing central mechanisms underlying audiogenic seizure activity and in studying functional properties and interactions of the central catechol-and indoleamine systems.
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PMID:Central action of a catechol-amide seizure-inducing agent: opposing effect on tyrosine and tryptophan hydroxylase activity in vivo. 0 34

In the long-term ovariectomized rat the secretion of LH has a pulsatile character. In such rats no difference was observed between morning and afternoon LH secretion. The administration of phenoxybenzamine, an chi-adrenergic blocker, resulted in depressed plasma LH levels. chi-Methyl-tyrosine (chi-MT), an inhibitor of tyrosine hydroxylase had no effect on plasma LH levels, whereas bis(4methyl-1-homopiperazinil-thiocarbonil) disulphide (FLA 63), an inhibitor of dopaminic-beta-hydroxylase, induced decreased plasma LH levels and disappearance of the pulsations. The same effect was observed after the administration of apomorphine, a dopaminic receptor stimulating drug, whereas the administration of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966), which blocks dopamine release, significantly raised plasma LH levels. Scopolamine, a cholinergic muscarinic receptor blocking drug, had no effect on plasma LH levels, whereas mecamylamine, a cholinergic nicotine receptor blocking agent, decreased them. These results are consistent with the hypothesis that the pulsatile release of LH in the long-term ovariectomized rat is caused by the stimulating activity of adrenergic and cholinergic, probably nicotinic, systems and the inhibitory activity of a dopaminergic system.
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PMID:Involvement of catecholaminergic and cholinergic mechanisms in the pulsatile release of LH in the long-term ovariectomized rat. 0 41

Rat striatal tyrosine hydroxylase is stimulated in vitro by various phospholipids. This stimulation was produced by a 3- to 4-fold increase in affinity for pteridine cofactor. No change in the Km for tyrosine was observed, The sedimentation pattern of tyrosine hydroxylase on linear sucrose gradients showed no indication of enzyme dissociation in the presence of lysolecithin at maximal stimulatory concentration. Crude striatal tyrosine hydroxylase is also activated by a combination of ATP, Mg++, EGTA and cAMP. After removing these agents by Sephadex G-25 chromatography, the activated form of the enzyme can be further stimulated by lysolecithin. These results suggest a possible role for phospholipids in the regulation of striatal dopamine synthesis.
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PMID:Stimulation of rat striatal tyrosine hydroxylase by phospholipids and adenosine-3',5'-monophosphate. 0 9

Inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine retarded growth and prevented melanization of limb regenerate in adult newts (Triturus cristatus).
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PMID:Production of retarded, albino, regenerates in newts by alpha-methyl-p-tyrosine. 0 68

Tyrosine hydroxylase (EC1.14.16.2), presumably the rate-limiting enzyme in the biosynthesis of catecholamines, is known to catalyze the hydroxylation of both phenylalanine and tyrosine. Using both an isolated enzyme preparation and a synaptosomal preparation, where some architectural integrity of the tissue has been preserved, we have attempted to evaluate the manner in which these two substrates are hydroxylated by rat brain tyrosine hydroxylase. In the presence of tetrahydrobiopterin the isolated enzyme catalyzes the hydroxylation of phenylalanine to 3,4-dihydroxyphenylalanine with the release of free tyrosine as an obligatory intermediate. In contrast, the rat brain striatal synaptosomal preparation in the presence of endogenous cofactor converts phenylalanine to 3,4-dihydroxyphenylalanine without the release of free tyrosine.
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PMID:Studies on phenylalanine and tyrosine hydroxylation by rat brain tyrosine hydroxylase. 0 89

By use of a sensitive and specific enzymatic isotopic method for the determination of tyramine, the small quantities of this amine which are present endogenously in rat tissues, including brain, heart, kidney and salivary gland, have been quantitated. The levels of tyramine in brain were increased to a similar extent by injecting animals with a monoamine oxidase inhibitor, pargyline, and a dopamine beta-hydroxylase inhibitor, FLA-63; in contrast, pretreatment of animals with alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, did not lead to an increase in tyramine levels in brain. Pretreatment of rats with 6-hydroxydopamine resulted in a marked diminution in the tyramine content of rat atria and salivary gland. Denervation of the salivary gland decreased the endogenous level of tyramine approximately 50% in denervated glands compared to undenervated glands. These results suggest that tyramine exists at least partly in sympathetic nerves in many tissues.
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PMID:Biosynthesis and metabolism of endogenous tyramine and its normal presence in sympathetic nerves. 1 Apr 24

Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.
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PMID:Catecholamine metabolism in neuroblastoma. 1 Apr 50

The sixth lumbar (L-6) ganglion has been used to study the central regulation of peripheral sympathetic neuron development. During post-natal ontogeny, tyrosine hydroxylase [tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] activity increased 60-fold, while total protein rose 10-fold in the ganglion. Transection of the spinal cord at the fifth thoracic (T-5) segment in neonatal rats prevented the normal developmental increase in tyrosine hydroxylase activity of the L-6 ganglion. However, spinal transection did not alter the ontogeny of tyrosine hydroxylase in the superior cervical ganglion, which derives its innervation from spinal segments rostral to the surgical lesion. Thus, spinal transection interfered with the maturation of sympathetic neurons distal to, but not proximal to, the lesion. The effect of transection on the L-6 ganglion persisted for at least one month, the longest time tested. Our observations suggest that trans-synaptic regulation of adrenergic maturation in the periphery is governed by suprasegmental mechanisms in the central nervous system.
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PMID:Central regulation of sympathetic neuron development. 1 May 72

The administration of choline in doses previously shown to elevate brain acetylcholine concentrations also increases the activity of tyrosine hydroxylase in rat caudate nuclei. This response can be blocked by atropine, a muscarinic antagonist. These findings indicate that choline-induced increases in acetylcholine concentrations may be associated with parallel changes in the amount of the neurotransmitter released into synapses.
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PMID:Choline administration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain. 1 Jun 29


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