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)

In vivo studies demonstrate that administration of gamma-butyrolactone, a precursor of gamma-hydroxybutyric acid causes a rapid increase in endogenous levels of striatal dopamine and an increase in tyrosine hydroxylase activity measured by following the short term accumulation of dihydroxyphenylalanine. The increase in dopamine produced by GBL is blocked by stimulation of the nigro-neostriatal pathway. If dopamine is allowed to accumulate for 30 min following administration of GBL this increased dopamine can be released by stimulation of the nigro-neostriatal pathway. Maintenance of neuronal activity in the nigro-neostriatal pathway by continuous stimulation at a physiological frequency of 3/s effectively blocks the ability of GBL to cause an increase in tyrosine hydroxylase activity in the striatum on the stimulated side. Tyrosine hydroxylase activity in the non-stimulated contralateral striatum is increased over 100% by administration of GBL. Stimulation of the nigro-neostriatal pathway 30 min after GBL administration causes about a 500% increase in the accumulation of dihydroxyphenylacetic acid in the striatum on the stimulated side. These results suggest that the increased dopamine is present in a pool which is releasable by neuronal stimulation and is subsequently exposed to MAO. These results are also consistent with the hypothesis that GBL activates tyrosine hydroxylase and increases endogenous dopamine levels primarily by blocking impulse flow in central dopaminergic neurons.
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PMID:Dopaminergic neurons: reversal of effects elicited by gamma-butyrolactone by stimulation of the nigro-neostriatal pathway. 1 82

l-Stepholidine (SPD) 2.5 and haloperidol (Hal) 1.0 mg.kg-1 ip increased rat striatal L-3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) accumulation induced by NSD 1015 (50 mg.kg-1, ip), a decarboxylase inhibitor. SPD (2.5 mg.kg-1, ip) did not alter but apomorphine (2.0 mg.kg-1, ip) decreased the dopamine (DA) content elevated by gamma-butyrolactone (GBL, 750 mg.kg-1, ip) in the rat striatum. Ip injection of either SPD 5.0 or Hal 2.5 mg.kg-1 after NSD 1015 50 mg.kg-1 or NSD 1015 plus GBL 750 mg.kg-1 also augmented tyrosine hydroxylase (TH) activity in the rat striatum. These results suggest that SPD produces an antagonistic effect on presynaptic DA receptors.
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PMID:Effects of l-stepholidine on tyrosine hydroxylase activity in rat corpus striatum. 136 Jul 40

Basal levels of endogenous 3,4-dihydroxyphenylalanine (DOPA) were detected by HPLC coupled with coulometric detection in dialysates from freely moving rats implanted 48-72 h earlier with transversal dialysis fibers in the dorsal caudate. Because decarboxylase inhibitor is absent in the Ringer's solution, this method allows monitoring of basal output of dopamine (DA) and 3,4-dihydroxyphenylacetic acid, as well as DOPA. Extracellular DOPA concentrations were reduced by the tyrosine hydroxylase inhibitor alpha-methylparatyrosine (200 mg/kg, i.p.) and by the dopaminergic agonist apomorphine (0.25 mg/kg, s.c.). The dopaminergic antagonist haloperidol (0.2 mg/kg, s.c.) stimulated DOPA output by about 60% over basal values. Gamma-Butyrolactone, at doses of 700 mg/kg, i.p., which are known to block dopaminergic neuronal firing and which reduce DA release, stimulated DOPA output maximally by 130% over basal values. Tetrodotoxin, which blocks DA release by blocking voltage-dependent Na+ channels, increased DOPA output maximally by 100% over basal values. The results indicate that basal DOPA can be detected and monitored in the extracellular fluid of the caudate of freely moving rats by transcerebral dialysis and can be taken as a dynamic index of DA synthesis in pharmacological conditions.
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PMID:Extracellular striatal concentrations of endogenous 3,4-dihydroxyphenylalanine in the absence of a decarboxylase inhibitor: a dynamic index of dopamine synthesis in vivo. 143 3

Reserpine depletes dopamine (DA) levels and increases tyrosine hydroxylase (TH) activity in the rat corpus striatum. TH is activated not only by enhancement of DA neuronal impulse flow, but also by cessation of impulse flow. To assist in the understanding of the relative contribution of impulse flow to the regulation of TH activity in the DA depleted neuron, we examined the consequences of severe DA depletion on substantia nigra DA neuronal impulse flow and on in vivo TH activity in the rat corpus striatum. One day after reserpine or 30 min after the reversible reserpine-like compound, Ro4-1284, striatal DA levels were severely depleted and in vivo TH activity was enhanced about three-fold. DA depletion was found to significantly increase DA neuronal impulse flow. Although the DA neuron is firing faster than normal in the DA depleted rat, because there is no DA being released it is still not clear whether the elevation in TH activity is due to the enhancement of impulse flow or to the lack of DA at presynaptic receptor sites, or both. gamma-Butyrolactone (GBL), causes a cessation of DA neuronal impulse flow and activates TH by a presynaptic autoreceptor mechanism. GBL inhibited by over 50 percent the elevation in TH activity produced by severe DA depletion. This finding suggests that the enhanced TH activation after DA depletion in in large part due to increased DA impulse flow. Furthermore, the TH activity seen with GBL in DA depleted rats was significantly less than that seen after GBL administration in normal rats. This finding is consistent with the hypothesis that the DA storage granule also plays a role in TH regulation.
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PMID:Effects of severe dopamine depletion on dopamine neuronal impulse flow and on tyrosine hydroxylase regulation. 611 Apr 70

Administration of methylazoxymethanol (MAM) in the fetal stage leads to forebrain microencephaly with a severe atrophy in cerebral cortex, striatum, and hippocampus. The concentration of endogenous monoamines was markedly increased in the atrophic regions while total amount was largely unchanged. Striatal dopamine and cortical noradrenaline nerve terminals from MAM treated animals showed unaltered sedimentation properties in a sucrose density gradient and were estimated to have normal transmitter levels. gamma-Butyrolactone induced increase in dopamine levels and its counteraction by apomorphine was essentially unaltered after MAM. These data give further support for the view that the monoamine nerve terminal fields develop to their normal size in the atrophic regions leading to a hyperinnervation. Analysis of monoamine metabolite levels, increase of monoamines after monoamine oxidase inhibition, and disappearance of catecholamines after tyrosine hydroxylase inhibition were conducted to obtain information on monoamine turnover. The results indicated an essentially unaltered, or a small reduction of, monoamine turnover in the atrophic regions when calculated per monoamine nerve terminal, while increased when calculated per unit weight of the tissue.
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PMID:Monoamine neurotransmitter metabolism in microencephalic rat brain after prenatal methylazoxymethanol treatment. 614 97

A chemical assay of tyrosine (Tyr) in nervous tissue is described. The method is based on a rapidly performed isolation of Tyr on small Sephadex G 10 columns, followed by reverse-phase HPLC in conjunction with amperometric detection. The method permitted the additional quantification of 3,4-dihydroxyphenylalanine, dopamine (DA), and its acidic metabolites. The method was applied to a study of the effects of gamma-butyrolactone, haloperidol, haloperidol in combination with amfonelic acid, morphine, NSD 1015, and tyrosine methylester on the concentration of Tyr in the striatum, frontal cortex, hypothalamus, and cerebellum of rat brain. The effect of tyrosine methylester on DA and its acidic metabolites was investigated in the striatum and frontal cortex. Morphine and NSD 1015 were found to increase Tyr levels. gamma-Butyrolactone, haloperidol, and haloperidol combined with amfonelic acid decreased the Tyr content in a manner related to their stimulatory effect on DA biosynthesis. These effects were restricted to DA-rich brain areas. It was concluded that during conditions of increased DA biosynthesis, the Tyr pool still possesses a considerable reserve capacity. The results bring into question the concept that brain Tyr is an important additional factor controlling catechol synthesis during increased tyrosine hydroxylase activity.
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PMID:On the significance of tyrosine for the synthesis and catabolism of dopamine in rat brain: evaluation by HPLC with electrochemical detection. 682 72

The effects of an in vivo electrical stimulation of the frontal cortex were measured on dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) contents in the striatum of rats anesthetized with chloral hydrate. Results showed a large decrease in DOPAC and a marked increase in DA content, similar to that obtained when nigrostriatal dopaminergic neuron firing rate is reduced by ?-butyrolactone (GBL) administration. If electrical activation of the corticostriatal glutamatergic neurons increased DA release into the striatum as previously shown in cats, the results of the present experiments actually appeared to be paradoxical. Further studies on [(3)H]DA uptake, tyrosine hydroxylase activity, and measurement of serotonin and 5-hydroxyindole acetic acid after cortical stimulation underline the specificity of changes in DA and DOPAC levels. These data may thus suggest that parallel changes in DA and DOPAC striatal contents can be obtained either by activating DA release by presynaptic mechanisms or by decreasing the firing rate of the nigrostriatal dopaminergic neurons.
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PMID:Comparative analysis of the effects of in vivo electrical stimulation of the frontal cortex and gamma-butyrolactone administration on dopamine and dihydroxyphenyl acetic acid (DOPAC) striatal contents in the rat. 2050 Oct 96