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)

Turnovers of dopamine (DA), norepinephrine (NE), epinephrine (E), and 5-hydroxytryptamine (5-HT) were determined in the brains of male turkeys during acute, chronic, and posttemperature stress. Changes induced in the depletion of endogenous monoamine levels 6 h after tyrosine hydroxylase or tryptophan hydroxylase inhibitions were regarded as changes in turnovers. High or low ambient temperature had no effect on brain DA turnover, whether the temperature stress was acute (6 h) or chronic (5 wk). Brain NE turnover increased upon acute exposure to either a cold (5 degrees C) or warm (32 degrees C) environment. Chronic exposure (5 wk) to such temperatures reduced significantly (P less than 0.001) the elevated NE turnover. The central E and 5-HT turnovers of birds kept at 32 degrees C for 6 h decreased and increased, respectively, whereas determination of E and 5-HT of birds kept at 5 degrees C showed an opposite pattern. Five weeks of continuous exposure to high and low environmental temperatures did not alter the changes in E and 5-HT turnovers from those observed during acute stress. Exposure of heat- or cold-reared turkeys to 24 degrees C reversed the changes in E and 5-HT turnovers. Thus the results indicated an increase in NE turnover only during acute exposure to thermal stress. However, the changes in E and 5-HT turnovers persisted during chronic exposure.
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PMID:Brain indole and catecholamines of turkeys during exposure to temperature stress. 13 76

Membrane-permeable derivatives of cyclic AMP (cAMP) produced concentration-dependent increases in activity of tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2) in membrane-limited nerve endings (synaptosomes) prepared from three regions of rat brain. Increased hydroxylation occurred even after preincubation and removal of dibutyryl cyclic AMP. In all brain regions, the hydroxylation of phenylalanine and tyrosine was increased, but dibutyryl cAMP had little effect on activity of tryptophan hydroxylase, no effect on aromatic amino-acid decarboxylase, on uptake of tyrosine or phenylalanine, uptake or efflux of dopamine, or distribution of hydroxylase between cytoplasmic and particulate components of the synaptosomes. Dibutyryl cAMP decreased inhibition of catecholamine synthesis in synaptosomes by dopamine and apomorphine. In a soluble preparation of striatal tyrosine hydroxylase, activity was increased by addition of lower concentrations of cAMP or dibutyryl cAMP than with unbroken nerve endings, when subsaturating concentrations of tyrosine and cofactor were employed, while butyrate, chloride, 5'-AMP, ADP, ATP, and cyclic GMP had no activating effect. Increased activity of soluble tyrosine hydroxylase was reflected in increased affinity (Km) for substrate and cofactor and decreased affinity (Ki) for inhibitory end-product (dopamine), suggesting a change in the physical-chemical state of the enzyme or an activator molecule. Cyclic AMP may activate tyrosine hydroxylase during periods of increased neuronal activity.
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PMID:Activation by cyclic 3':5'-adenosine monophosphate of tyrosine hydroxylase in the rat brain. 23 58

After rats were trained to differentiate between the effects of d-amphetamine and saline in a state-dependent task, pretreatment with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, significantly decreased amphetamine discrimination. Pretreatment with the dopamine-beta-hydroxylase inhibitor, disulfiram, or with the tryptophan hydroxylase inhibitor, p-chloro-phenylalanine, was observed to have no effect on the rats' ability to discriminate d-amphetamine. Administration of haloperidol, a selective dopamine receptor blocker, completely abolished the amphetamine discrimination, whereas alpha- and beta-adrenergic receptor blockade had no effect. Apomorphine, a dopamine receptor stimulant, produced amphetamine-like responses and this was, likewise, abolished by pretreatment with haloperidol. These data suggest that dopaminergic systems mediate the interoceptive cue produced by d-amphetamine in rats, and these results are discussed in relation to possible dopamine mediation of amphetamine psychosis and paranoid schizophrenia.
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PMID:Dopaminergic mediation of the interoceptive cue produced by d-amphetamine in rats. 24 Jan 81

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

Daily treatment of neonatal rats with 1-triiodothyronine for 30 days increased locomotor activity as well as the synthesis and presumably, release of brain norepinephrine, dopamine and 5-hydroxytryptamine. Whereas administration of lithium carbonate (60 mg/kg) to normal rats for 10 days, beginning from the 20th day of age, produced no significant effect, this antimanic drug significantly decreased the observed increase in spontaneous locomotor activity in l-triiodothyronine-treated rats. Lithium treatment in normal rats increased the activity of striatal tyrosine hydroxylase, but produced no significant effect on the endogenous levels of norepinephrine and dopamine in several discrete brain regions examined. Lithium, enhanced deamination of catecholamines as evidenced by increased level of 3,4-dihydroxyphenylacetic acid and monoamine oxidase activity in normal rats. The activity of catechol o-methyltransferase was decreased to 82 and 59% in midbrain and crebral cortex of normal rats, respectively. Furthermore, chronic treatment with lithium increased endogenous levels of tryptophan, tryptophan hydroxylase, 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, in normal animals. In contrast to the effects seen in normal rats, admininstration of lithium in l-triiodothyronine-treated animals significantly decreased tyrosine hydroxylase as well as dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid, suggesting that this antimanic drug reduced the synthesis and turnover of dopamine. However, the steady-state levels of norepinephrine were raised in hypothalamus, pons-medulla, midbrain and striatum of lithium-treated hyperthyroid rats. As seen in normal animals, lithium in l-triidothyronine-treated rats increased trytophan, tryptophan hydroxylase and 5-hydroxytryptamine levels, but decreased the concentration of 5-hydroxyindoleacetic acid. The results show that the suppressed behavioral activity seen in lithium-treated hyperthyroid rats may be associated with decreased synthesis of norepinephrine and dopamine in the brain. Finally, the effects exerted by lithium on the brain catecholamine metabolizing system of young hyperthyroid rats were not similar to those seen in normal rats of the corresponding age group.
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PMID:Lithium: modification of behavioral activity and brain biogenic amines in developing hyperthyroid rats. 85 Jan 49

In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats. Whereas administration of l-triiodothyronine (10 mug/100 g/day) for 30 days to 120-day-old rats increased the levels of tyrosine by 23% and of tryptophan by 43%, no appreciable change was noted in tryptophan hydroxylase activity. In contrast to neonatal hyperthyroidism, excess of thyroid hormone in adult rats failed to produce any change in motor activity and tended to decrease striatal tyrosine hydroxylase activity only slightly. The concentration of dopamine remained unchanged in all regions of the brain except in midbrain where it rose by 19%. Whereas norepinephrine concentration was altered in hypothalamus, pons-medulla and midbrain, the levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, were significantly decreased in striatum and cerebellum. Since dopaminergic and noradrenergic neurons are the critical components of the motor system, the possibility exists that elevated behavioral activity in young L-triiodothyronine-treated animals might be associated with increased turnover of catecholamines in neuronal tissue.
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PMID:Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain. 97 62

The possible implication of central catecholamines in the phasic phenomenon of ponto-geniculo-occipital (PGO) waves was investigated using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 (=PGO(1284), and the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (=PGO(PCPA); they were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in a previous report. The effect on PGO(1284) and PGO(PCPA) of various drugs interacting with the different steps of catecholaminergic transmission was studie. Injections of noradrenaline (NA) and of dopamine (DA) into the lateral brain ventricle tended to decrease the density of PGO(1284). The stimulant of central alpha-adrenoceptors, clonidine, suppressed PGO(1284) and PGO(PCPA) in very small doses. Apomorphine in high doses had inconsistent depressant effects which were probably not related to its stimulant action on DA receptors. Release of brain NA by dexamphetamine and beta-tetrahydronaphthylamine decreased the density of PGO waves, alpha-Methyldopa diminished PGO(PCPA) but not PGO(1284. The MAO-inhibitor, nialamide, depressed PGO(PCPA) more than PCO(1284), whereas pheniprazine was inactive. The inhibitor of catechol-O-methyltransferase, tropolone, reduced the density of bially blocks the uptake of NA, was more potent on PGO(PCPA) than on PGO(1284). The alpha-adrenoceptor blocking agent, phenosybenzamine, markedly increased the density of PGO(PCPA). Similar effects were obtained with thioridazine and clozapine, which aare also known to be blockers of central alpha-adrenoceptors. Inhibition of tyrosine hydroxylase (by alpha-methyltyrosine) and of DA-beta-hydroxylase (by disulfiram or Ro 8-1981), in addition to the inhibition of tryptophan hydroxylase by PCPA, induced PGO waves comparable in density and temporal distribution to those occurring following the application of Ro 4-1284. The acute bilateral lesion of the dorsal and caudal parts of thel ocus coeruleus increased the density of PGO(PCPA). The results strongly suggest that, in addition to the 5-hydroxytryptaminergic system, noradrenergic neurones, probably originating in the locus coeruleus, depress the neurones in the pontine reticular formation involved in the generation of PGO waves.
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PMID:Drugs and PGO waves in the lateral geniculate body of the curarized cat. III. PGO wave activity and brain catecholamines. 127 19

The behavior of rats with selective lesions of either the dorsal (B7), median (B8), or lateral (B9) raphe nuclei was compared to that of sham-lesioned controls in a variety of experimental situations. As described previously, the extent of damage to the midbrain raphe nuclei was determined by fluorescence histochemistry, and the tryptophan hydroxylase and tyrosine hydroxylase activities of 6 forebrain regions were measured for each rat. None of the lesions affected tyrosine hydroxylase activity. Lesions of B7, which reduced tryptophan hydroxylase in the striatum, thalamus, cortex, and hypothalamus, had no significant effect on any of the behavioral measures. Lesions of B9, although twice as large, neither reduced forebrain tryptophan hydroxylase significantly nor affected any of the behavioral variables. However, B8 lesions, which reduced hippocampal, septal, cortical, and hypothalamic tryptophan hydroxylase, had behavioral effects similar to those reported after combined raphe lesions parachlorophenylalanine. Median raphe-lesioned rats were hyperactive when placed in a novel environment and throughout the dark phase of the light/dark cycle. With respect to locomotor activity, B8-lesioned rats were also hyper-responsive to amphetamine. When placed in a stabilimeter and subjected to repeated air puff stimuli, rats with B8 lesions exhibited larger startle responses. Furthermore, only B8-lesioned animals perseverated when given two unreinforced trials in a Y-maze. All these histologic, biochemical, and behavioral variables were assessed individually for all 39 animals, and a multivariate correlational analysis incorporating the data of this and the preceding paper is presented here. These experiments suggest that the mesolimbic serotonergic pathway originating in B8 subserves some of the inhibition necessary to dampen behavioral responsivity.
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PMID:Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways. 127 71

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation-increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R-THBP and methamphetamine by changing the time-of-day of both methamphetamine administration and pretreatment with R-THBP. The mouse's ambulatory activity was measured by a tilting-type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation-increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R-THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R-THBP increases the biosynthesis of catecholamine especially in the daytime.
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PMID:Circadian variation in R-THBP-induced enhancement of the ambulation-increasing effect of methamphetamine on mice. 130 21

Cortical choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), muscarinic receptors and sodium-dependent, high-affinity, choline uptake (SDHACU) sites were examined in the rat brain following unilateral stereotaxic injection of the cholinotoxin, AF64A, into the nucleus basalis magnocellularis (NBM). Injection of AF64A resulted in a significant loss of presynaptic cholinergic markers in the cortex without alteration in TH and TPH activity. The binding to SDHACU sites was reduced to background values in the NBM and increased in the central amygdala (Ce) and cortex. The increase in cortical [3H]QNB binding was the result of a change in muscarinic receptor number (BMAX) and not a change in receptor affinity (KD). Examination of muscarinic receptor subtypes demonstrated a reduction of M1 receptor binding in the cortex and NBM without any alteration in the Ce. Non-M1 binding was significantly increased in all the laminae of the cortex and in the Ce, but decreased in the NBM. These data suggest that there exists a population of M1 receptors on NBM projections to the cortex and that NBM projections influence a population of postsynaptic receptors in the cortex and Ce which are not of the M1 subtype.
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PMID:Alterations in cortical muscarinic receptors following cholinotoxin (AF64A) lesion of the rat nucleus basalis magnocellularis. 134 2


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