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)

Acute administration of cocaine (20 mg/kg, i.p.) stimulated activity of striatal tyrosine hydroxylase (TH) which reached its maximum level at 10 min and returned to normal between 20-40 min. However, tryptophan hydroxylase (TPH) activity in the pons-medulla was reduced to a minimum at 10 min after its injection and returned to normal between 20-40 min. Activity of monoamine oxidase (MAO) was significantly reduced at 10 min and increased MAO (Type A) at 20 min showing a biphasic effect of cocaine on this enzyme. Relation of the time-courses of cocaine effects on the activity of these enzymes and the levels of related neurotransmitters is discussed.
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PMID:Effect of cocaine on rat brain enzymes. 614 75

A new microbial inhibitor for rat-liver phenylalanine hydroxylase (L-phenylalanine, tetrahydropteridine: oxygen oxidoreductase (4-hydroxylating), EC 1.14.16.1) was isolated from a culture medium of Fomes tasmanicus, and its structure was determined as 3,4-dihydroxystyrene. This compound inhibited the enzyme by 50% at a concentration of 5 X 10(-6) M and 5 X 10(-7) M, respectively, without or with preincubation at 25 degrees C for 15 min. Without preincubation, dihydroxystyrene inhibited phenylalanine hydroxylase noncompetitively with phenylalanine and a pteridine cofactor, 6,7-dimethyltetrahydropterin, and uncompetitively with oxygen. A change in kinetic properties of the inhibition was observed when the enzyme was preincubated with dihydroxystyrene; the degree of inhibition was increased, and the purely noncompetitive-type inhibition with phenylalanine changed to a mixed-type inhibition. A study concerning the structure-inhibitory activity relationship using several compounds similar to dihydroxystyrene, indicated that the catechol structure is essential and that the structure of the aliphatic side-chain affects the inhibitory potency. A similar degree of inhibition was observed using 6,7-dimethyl- or 6-methyltetrahydropterin or tetrahydrobiopterin as a cofactor. Dihydroxystyrene also inhibited other pteridine-dependent monooxygenases, tyrosine hydroxylase (EC 1.14.16.2) and tryptophan hydroxylase (EC 1.14.16.4), indicating that dihydroxystyrene is a general inhibitor for pteridine-dependent monooxygenases.
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PMID:3,4-dihydroxystyrene, a novel microbial inhibitor for phenylalanine hydroxylase and other pteridine-dependent monooxygenases. 614 5

A single dose (17.5 mg/kg i.p.) of methamphetamine was administered to iprindole-treated (10 mg/kg i.p.) rats. Forebrain concentrations of methamphetamine and amphetamine were significantly increased in iprindole-treated rats 1 and 6 hr after injection; in contrast to rats pretreated with saline, both amines were also detected after 18 hr. Three and 7 days after injection, significant decreases were seen in tryptophan hydroxylase (TPH) activity and serotonin concentrations in the cerebral cortex, neostriatum and hypothalamus. Hypothalamic TPH activity had recovered by 14 days. Neostriatal tyrosine hydroxylase activity and dopamine concentrations were significantly depressed at all time points examined. Iprindole alone produced a significant increase in cortical TPH activity after 1 day. After 3 days, TPH activity was significantly decreased when compared with control, whereas serotonin and 5-hydroxyindoleacetic acid concentrations were significantly increased. This study demonstrates that persistence of methamphetamine and/or amphetamine at the site of action is important for neurotoxicity.
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PMID:Effects of a single dose of methamphetamine and iprindole on the serotonergic and dopaminergic system of the rat brain. 618 15

Rats treated with iprindole (IPR) (10 mg/kg, i.p.) were given a single dose (15 mg/kg, i.p.) of amphetamine (AMP). Marked decreases in the activity of tryptophan hydroxylase (TPH) were observed in both the cerebral cortex and neostriatum after 6 hr, with maximum depression observed at 24 hr. Enzyme activity had returned to control levels in neostriatum after 3 days and in cerebral cortex after 7 days. Levels of serotonin (5-HT) in both the cerebral cortex and neostriatum were significantly lowered at 24 hr but had recovered by 72 hr. Levels of tryptophan (TRP) in the cortex were significantly elevated after 6 hr, recovering by 24 hr. In the neostriatum, the activity of tyrosine hydroxylase (TH) was significantly depressed by 24 hr and remained so for 7 days. Concentrations of dopamine (DA) were decreased at all times examined. This study clarifies the differences previously observed in the response of the serotonergic system to amphetamine or methamphetamine (METH) in iprindole-treated rats.
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PMID:The effects of a single dose of amphetamine and iprindole on the serotonergic system of the rat brain. 620 34

Repeated administration of large doses of d-methamphetamine produce long-lasting depletion of brain dopamine (DA) and serotonin (5-HT), as well as persistent decreases in the activity of their respective biosynthetic enzymes, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH). The present results indicate that the inhibitor of 5-HT uptake fluoxetine, prevented the long-term depletion of 5-HT produced by large doses of methamphetamine (15 mg/kg X 5, 6 hr apart) in the neostriatum and hippocampus, while simultaneously augmenting the depletion of DA produced by this drug in the neostriatum. Fluoxetine also enhanced the prolonged neostriatal depletion of DA produced by a comparable regimen of d-amphetamine. In these doses (15 mg/kg X 5,6 hr apart), d-amphetamine did not produce long-lasting depletion of 5-HT in either the neostriatum or hippocampus. Larger depletion of DA after the amphetamines had been administered in the fluoxetine pretreated animal were associated with a transient increase in the brain levels of methamphetamine and amphetamine. This suggests that fluoxetine may inhibit the metabolism of amphetamines.
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PMID:Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphetamine and d-amphetamine. 660 37

Phenylalanine hydroxylase activity measured in leucocytes and fibroblasts by the fluorometric method is nonspecific and can be released by other aromatic hydroxylases. Investigations with the inhibitors p-Cl-phenylalanine, 3-I-tyrosine and 6-F-tryptophan made evident that these results may be caused by the tryptophan hydroxylase and the tyrosine hydroxylase. Phenylalanine hydroxylase activities in leucocytes could also not be measured by radiochemical investigations with [3-14C] phenylalanine (scanner and liquid scintillation technique).
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PMID:[Detection of phenylalanine hydroxylase activity in leukocytes and fibroblasts]. 667 Sep 99

The rapidity, simplicity and reproducibility of the rapid glyoxylic acid technique (SPG) has made it the method of choice for many investigators interested in the histofluorescence of CNS catecholamine systems. Unfortunately, the serotonergic system and the dopaminergic hypothalamic cell groups are poorly visualized with this method. Using intraventricular colchicine pretreatment, reliable visualization of these systems can be obtained. The serotonergic fluorescence seen with colchicine administration is augmented by l-tryptophan pretreatment and diminished by pretreatment with para-chlorophenylalanine, a tryptophan hydroxylase inhibitor. It is relatively resistant to fading under ultra-violet illumination and photographs can be taken up to 4 weeks after the sections have been processed. Visualization of dopaminergic, hypothalamic neurons as well as visualization of the dendritic fields of all catecholaminergic neurons is comparable to that obtained with tyrosine hydroxylase immunocytohistochemistry.
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PMID:A modification of the rapid glyoxylic acid technique permits visualization of serotonergic and hypothalamic dopaminergic neurons. 675 Feb 55

1 The effects of low-dose lithium administration (2 mEq/kg, daily) and its subsequent withdrawal have been examined with reference to changes in biogenic amine systems in several discrete regions of rat brain. 2 Increased levels of striatal tyrosine and midbrain tryptophan were found following lithium administration together with slight decreases in striatal tyrosine hydroxylase and midbrain tryptophan hydroxylase activities. Withdrawal resulted in a decrease in tyrosine content with increased tyrosine hydroxylase activity, whilst tryptophan levels and tryptophan hydroxylase activity were increased. 3 Lithium treatment and withdrawal resulted in altered levels of noradrenaline and dopamine, these changes being regionally variable. 3-Methoxy-4-hydroxyphenylglycol content was depressed in both treated and withdrawal rats as were 3,4-dihydroxyphenylacetic acid levels. Homovanillic acid decreased as a result of lithium treatment, but was greatly elevated in the withdrawal group. 4 5-Hydroxytryptamine content decreased in some brain regions following lithium treatment with return towards control values in withdrawal rats. 5-Hydroxyindoleacetic acid levels also displayed a regional variation as a result of lithium treatment and withdrawal. 5 The implications of these observations in elucidating the pharmacological effect of lithium treatment and its subsequent withdrawal are discussed.
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PMID:Effect of low-dose lithium administration and subsequent withdrawal on biogenic amines in rat brain. 719 96

We have examined several aspects of neurotransmitter function in the brains of mice carrying a deletion mutation in the gene encoding the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). During the first 6 weeks of postnatal development, dopamine levels in whole-brain extracts from the mutant mice (HPRT-) failed to increase at rates comparable to normal animals, resulting in 40% lower dopamine levels throughout adulthood. Regional analysis in adult animals showed the caudoputamen to be the most severely affected region, with dopamine deficits of 48-64%. Dopamine levels in other regions were normal or less severely affected. The decrease in dopamine was accompanied by a decrease in tyrosine hydroxylase (TH) activity, the rate-limiting step in dopamine synthesis. Kinetic analysis of TH extracted from the caudoputamen of normal and HPRT- mice demonstrated a 45% decrease in Vmax with an increased affinity for the tetrahydropterin cofactor in the mutants. Labeling of midbrain dopamine neurons using TH immunohistochemistry revealed no obvious deficits in the number of midbrain dopamine neurons, but quantitative autoradiographic studies revealed significant reductions in the binding of 3H-N-[1-(2-benzo(beta)thiophenyl)cyclohexyl]piperidine (3H-BTCP) to dopamine uptake sites in the forebrain of the mutants. In contrast to these abnormalities of the dopamine systems in the mutant mice, other neurotransmitter systems appeared relatively unaffected. Norepinephrine, 5-HT, tryptophan hydroxylase, and glutamic acid decarboxylase were present at normal levels in the brains of the mutants. ChAT activity was slightly lower than normal in the caudoputamen of the mutant animals, but was normal in all other brain regions examined. These results indicate that HPRT deficiency is associated with a relatively specific deficit in basal ganglia dopamine systems that emerges during the first 2 months of postnatal development.
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PMID:Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease. 750 65

Hypothalamic dopaminergic periventricular and arcuate nuclei are known to project to the pituitary gland and contain serotonin in their terminals. In order to elucidate the potential of these neurons to synthesize serotonin, we studied immunohistochemically the possible tryptophan hydroxylase content of periventriculo-hypophyseal neurons, identified by retrograde tracing from the pituitary gland. These neurons were found to contain tryptophan hydroxylase-immunoreactivity (TpOH-IR), which was enhanced after colchicine treatment. All of the TpOH-IR neurons contained tyrosine hydroxylase-immunoreactivity as well. However, none of them were immunoreactive for serotonin in either intact animals or in animals pretreated with serotonin precursor L-tryptophan and MAO inhibitor pargyline. Thus, neurons of the dopaminergic periventriculo-hypophyseal pathway express tryptophan hydroxylase, but are unable to synthesize serotonin. These findings (i) raise the possibility that, in these nerves, serotonin might serve a function other than regular synaptic transmission, and (ii) suggest that expression of an enzyme synthesizing certain transmitter does not necessarily confirm the corresponding transmitter phenotype of that neuron.
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PMID:Dopaminergic periventriculo-hypophyseal nerves show tryptophan-hydroxylase immunoreactivity but lack serotonin synthesis. 758 7


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