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)

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

Tyrosine and tryptophan hydroxylase activity was studied in the postnatal rat brain in vivo by measuring the accumulation of dihydroxyphenylalanine and 5-hydroxytryptophan, respectively after inhibition of L-aromatic amino acid decarboxylase with NSD 1015. With increasing age there was a significant increase in the amount of dopa and 5-HTP accumulated in the brain after administration of NSD 1015. After 30 min in a 12% oxygen environment there were significant reductions of tyrosine hydroxylase and tryptophan hydroxylase activity at 1,14 and 28 but not 4 days of postnatal age. Further, the decrease in 5-HTP accumulation was significantly more marked at 14 and 28 days than at 1 day of age. Thus, the oxygen-dependent synthesis of the neurotransmitter 5-hydroxytryptamine seems to be less vulnerable in the early postnatal rat brain.
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PMID:Effect of hypoxia on monoamine synthesis in brains of developing rats. 1 38

Biochemical parameters in the brains of olfactory bulbectomized male and female mice were studied in two experiments, followed by three experiments in which 5-HTP was injected into bulbectomized males and females to try to block abnormal behaviors. In Experiment 1 bulbectomized male and female mice had significantly less tryptophan hydroxylase in their brains than did sham controls. Neither 5-hydroxtryptophan decarboxylase nor tyrosine hydroxylase activity was affected. In Experiment 2 the rate of synthesis of 5-HT was significantly less in bulbectomized males and females. Since bulbectomy leads to increased pup killing by female mice, the objective of Experiments 3 and 4 was to see whether the injection of 5-HTP into bulbectomized females could block this behavior. The incidence of pup killing was not influenced, but in both studies the latency to kill was significantly prolonged. Olfactory bulbectomy eliminates aggressive behavior in male mice, and the purpose of Experiment 5 was to determine whether 5-HTP treatment could restore normal levels of aggression. No significant effect was found. The data suggest that a dual mechanism is needed to explain the behavioral abnomalities seen in the two sexes; the mechanism in the female appears to be serotonergic while that in the male is still unknown.
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PMID:Influence of olfactory bulbectomy and the serotonergic system upon intermale aggression and maternal behavior in the mouse. 24 12

6-Hydroxydopamine (6-OHDA) treatment of neonatal rats resulted in a dose-related loss of striatal dopamine (DA). These reductions corresponded closely with the loss of tyrosine hydroxylase-containing terminals at this brain site. Striatal serotonin (5-HT) concentration increased only after DA was maximally depleted by the highest dose of 6-OHDA. Quantitative immunohistochemistry revealed that the increased 5-HT content after neonatal 6-OHDA lesioning was due to a proliferation of 5-HT nerve terminals. The density of immunoreactive 5-HT-containing terminals appeared to increase more than did the 5-HT content. The present study examined whether 5-HT hyperinnervation was playing a role in behavioral responses induced by D1-DA agonists and antagonists in neonatally lesioned rats, because reports have suggested that these drugs may interact with 5-HT receptors. However, SCH-23390, the D1-DA antagonist (0.3 mg/kg), did not alter behavioral responses to 5-HTP and SKF-38393 (3 mg/kg), a D1-DA agonist did not produce any signs of activating 5-HT receptors in 5,7-DHT-lesioned rats. These data indicate that these compounds affecting D1-DA receptors do not have a significant effect on 5-HT function at doses which have maximal effects on D1-DA receptor function. Pretreatment with the 5-HT antagonist methysergide did not produce a change in apomorphine-induced locomotion and did not antagonize the self-mutilation or the other behaviors produced by L-DOPA or SKF-38393 in neonatally lesioned rats, suggesting that 5-HT hyperinnervation is not responsible for these drug-induced changes in neonatal 6-OHDA-lesioned rats.
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PMID:Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: an anatomical, biochemical and pharmacological study. 257 38

The time course of the variations in tyrosine hydroxylase activity (THA) and serotonin (5-HT) content were measured in the rat locus coeruleus after parachlorophenylalanine (PCPA) administration. Highly significant decreases in the 5-HT content in LC were found 24-48 h after PCPA treatment (300 mg/kg daily). An increase in THA (in the LC) was found to be significant 4 days after 2 successive injections of PCPA and after 4 successive injections of the drug THA gradually increased, reaching a maximum around 4 days after the last injection. This maximum increase in THA was greatly reduced when 5-HTP was simultaneously administered with PCPA. These results join others which suggest that a serotonin-mediated mechanism could be one of the processes controlling noradrenaline metabolism in the locus coeruleus.
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PMID:Alteration of tyrosine hydroxylase activity in the locus coeruleus after administration of p-chlorophenylalanine. 610 35

Regional changes in the rate of brain monoamine synthesis were monitored in male rats exposed to, but prevented from physical contact with, an estrous or an ovariectomized female. The in vivo rate of tyrosine and tryptophan hydroxylase activities were estimated by measuring the accumulation of DOPA and 5-HTP following inhibition of cerebral aromatic L-amino acid decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015) treatment (100 mg/kg i.p.). 5 min upon NSD-1015 treatment, the males were exposed to an intact estrous female or an ovariectomized female for 20 min before decapitation and brain dissections. Exposure to an estrous female produced an increased rate of tyrosine and tryptophan hydroxylase activity in the medial prefrontal cortex, the dorso-lateral neostriatum and in the ventral neostriatum, in comparison with home-cage controls. By the same comparison, exposure to an ovariectomized female resulted in an increased rate of tyrosine hydroxylase activity in the medial prefrontal cortex, but not in the neostriatal areas, whereas tryptophan hydroxylase activity was unaffected. Finally, exposure to the empty test cage, with no stimulus females present, did not produce any statistically significant changes in the rate of tyrosine or tryptophan hydroxylase activity in any of the brain areas sampled. Taken together with recent findings from this laboratory, the present results demonstrate that the level of sexual motivation brought about by the olfactory, auditory and/or visual stimulation of a receptive female is associated with an increased demand on catecholamine and 5-hydroxytryptamine synthesis in the limbic forebrain of the male rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of exposure to an estrous female on forebrain monoaminergic neurotransmission in the non-copulating male rat. 811 7

Exposure of female catfish, Heteropneustes fossilis to 30-day regimes of long photoperiod (16L), elevated temperature (28 +/- 2 degrees C), or a combination of both stimulated brain tyrosine hydroxylase (TH) activity significantly over that of control fish held in natural conditions in gonad resting (10.5L:13.5D, 10 +/- 2 degrees C) and preparatory (12.5L:11.5D,18 +/- 2 degrees C) phases. The response was high in the combination group in both phases. The increase in TH activity was higher in forebrain regions (telencephalon and hypothalamus) than medulla oblongata. Exposure of the fish to short photoperiod (8L:16D) and total darkness decreased the enzyme activity significantly in both resting and preparatory phases regardless of the temperature. The inhibition was high in fish held under total darkness. Gonadosomatic index (GSI) was significantly elevated in long photoperiod and high temperature groups, alone or in combination, and decreased significantly in short photoperiod (only in preparatory phase) and total darkness groups. Administration of the serotonin precursor 5-hydroxytryptophan (5-HTP; 5mg/100g body weight [BW], three daily intraperitoneal [i.p.] injections prior to sacrificing) stimulated TH activity in fish held under long and normal photoperiods in both phases. Three daily injections of the serotonin blocker parachlorophenylalanine (p-CPA; 10mg/100g BW) and melatonin (75 microg/100g BW) prior to sacrificing inhibited brain TH activity significantly in both phases. GSI was significantly stimulated by 5-HTP, and inhibited by both p-CPA and melatonin injections. Changes in TH activity and GSI can be correlated and explained on the basis of previous reports on changes in catecholamine activity that modulates gonadotropin secretion in the catfish. Further, the photoperiod and temperature-induced changes in TH activity may be modulated by alterations in serotonergic activity.
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PMID:Effects of altered photoperiod and temperature, serotonin-affecting drugs, and melatonin on brain tyrosine hydroxylase activity in female catfish, Heteropneustes fossilis: a study correlating ovarian activity changes. 1241 Jun 7

5-Hydroxytryptophan (5-HTP), which is the rate-limiting precursor in serotonin (5-hydroxytryptamine (5-HT)) biosynthesis, is used as an oral supplement to enhance serotonin levels in humans. To evaluate its effects on serotonin levels and localization, 5-hydroxytryptophan was administered to Sprague-Dawley rats either orally or via intraperitoneal injection. 5-Hydroxytryptophan-immunoreactivity was co-localized with serotonin-immunoreactivity in the serotonergic dorsal raphe nucleus of control animals and this was not changed in animals given 5-hydroxytryptophan. Oral 5-HTP administration increased the intensity of both 5-HTP and serotonin immunoreactivity in raphe neurons. However, 5-HTP treatment also caused ectopic 5-hydroxytryptophan-immunoreactivity and serotonin-immunoreactivity in normally dopaminergic neurons of the substantia nigra par compacta. Serotonin-immunoreactivity was confined to neurons that also displayed amino acid decarboxylase immunoreactivity, but in a small percentage of substantia nigra neurons, serotonin immunoreactivity was not co-localized with tyrosine hydroxylase-immunoreactivity. The intensity of the immunoreactivity to serotonin and 5-hydroxytryptophan in the substantia nigra was maximal within 2h of 5-hydroxytryptophan administration and returned to control levels by 24h. This time course mirrored changes in HPLC measurements of 5-hydroxytryptophan, serotonin, and the metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the urine. 5-Hydroxytryptophan administration did not cause ectopic appearance of either serotonin or 5-hydroxytryptophan in the noradrenergic locus coeruleus. These results suggest that a single oral dose of 5-HTP increases the 5-HTP and serotonin content of serotonergic neurons and causes the transient ectopic appearance of serotonin in some normally non-serotonergic neurons.
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PMID:The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats. 1512 Dec 17

The effects of daily late afternoon administration of the indoleamine, melatonin, on the in situ activity of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) were examined in the caudate nuclei of the striatum of male Syrian hamsters. TH and TPH activities were determined in tissue extracts by measuring the accumulation of L-Dopa and 5-HTP respectively, following the administration of the aromatic L-amino acid decarboxylase inhibitor, NSD-1015. Animals were sacrificed at 4 time points over the 24 light/dark cycle after 9.5 weeks of melatonin treatment. TH activity was significantly increased by melatonin during the early part of the dark phase of the light/dark cycle. While no significant effects of melatonin on TPH was observed, melatonin significantly increased 5-HT concentrations, suggesting a melatonin-induced inhibition of 5-HT release. The data suggest that the striatum may be a region in which dopaminergic neurons are subject to significant regulation by melatonin, either directly or through serotonergic neurons which synapse on dopaminergic neurons in the striatum.
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PMID:Melatonin: effects on dopaminergic and serotonergic neurons of the caudate nucleus of the striatum of male Syrian hamsters. 1706 55

In contrast to monoaminergic (MA-ergic) neurons possessing the whole set of the enzymes for MA synthesis from the precursor amino-acid, some, mostly peptidergic, neurons co-express only one of the enzymes of monoamine synthesis. They are widely distributed in the brain, being particularly numerous in ontogenesis and, in adulthood, under certain physiological conditions. Most monoenzymatic neurons possess one of the enzymes for dopamine (DA) synthesis, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). TH and AADC are enzymatically active in a substantial number of monoenzymatic neurons, where they are capable of converting L-tyrosine to L-3,4-dihydroxy-phenylalanine (L-DOPA) and L-DOPA to dopamine (DA) (or 5-hydroxy-tryptophan, 5-HTP to serotonin), respectively. According to our data L-DOPA synthesized in monoenzymatic TH-neurons is released and taken up by monoenzymatic AADC-neurons for DA synthesis. Moreover, L-DOPA captured by dopaminergic neurons and serotoninergic neurons serves to stimulate dopamine synthesis in the former and to start DA synthesis in the latter. Cooperative synthesis of MAs is considered as a compensatory reaction under a failure of MA-ergic neurons, e.g. in neurodegenerative diseases like hyperprolactinemia and Parkinson's disease, which are developed primarily because of degeneration of DA-ergic neurons of the tuberoinfundibular system and the nigrostriatal system, respectively. Noteworthy, the neurotoxin-induced increase of prolactin secretion returns with time to a normal level due to the stimulation of DA synthesis by the tuberoinfundibular most probably monoenzymatic neurons. The same compensatory mechanism is supposed to be used under the failure of the nigrostriatal DA-ergic system that is manifested by an increased number of monoenzymatic neurons in the striatum of animals with neurotoxin-induced parkinsonism and in humans with Parkinson's disease. Expression of the enzymes of MA synthesis in non-monoaminergic neurons is controlled by intercellular signals such as classical neurotransmitters (catecholamines), etc. Thus, a substantial number of brain neurons express partly the monoaminergic phenotype, namely individual complementary enzymes of MA synthesis, serving to produce MAs in cooperation, which is considered as a compensatory reaction under the failure of MA-ergic neurons.
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PMID:[Synthesis of monoamines by non-monoaminergic neurons: illusion or reality?]. 1935 13


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