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)

Administration of a single dose (10 mg/kg) of a relatively new benzodiazepine, bromazepam to rats markedly suppressed their spontaneous locomotor activity. Hypomobility became apparent 15 min after the injection and remained significantly lower during the period of observation for 6 hours when locomotor activity was 27% of controls. Following 2 hours after bromazepam treatment, no change was noted in tyrosine levels and tyrosine hydroxylase activity in striatum or rate of catecholamine synthesis in synaptosomal preparation (P2 pellet). However, the endogenous levels of norepinephrine, dopamine and 5-hydroxytryptamine were significantly increased not only in several brain areas examined, but also in P2 pellet. Bromazepam failed to change 3H-norepinephrine and 3H-5-hydroxytryptamine uptake in synaptosomes suggesting that the increased levels of monoamines are not related to laterations in uptake mechanisms, but probably to a diminished release. This is supported by the data on striatal homovanillic acid and whole brain 4-hydroxy-3-methoxyphenyl glycol whose concentrations were significantly lowered following a single injection of this benzodiazepine. However, bromazepam increased 5-hydroxyindole-acetic acid levels in hypothalamus, mid-brain and pons-medulla. The present study demonstrates that bromazepam elicits its tranquilizing action by lowering the release of catecholamines in brain; however, its anti-anxiety action might be associated with a reduction in 5-hydroxytryptamine turn over. Our data also suggest that bromazepam is almost as potent as diazepam in altering the metabolism of certain putative neurotransmitters in brain.
 ...
PMID:Effect of a new benzodiazepine bromazepam on locomotor performance and brain monoamine metabolism. 2 78

Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.
 ...
PMID:Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings. 4 9

The precursors tyrosine and tryptophan as well as the synthesizing and deaminating enzymes of catecholamines have been identified in methylcholanthrene-induced prostatic carcinoma of rats. Tyrosine hydroxylase, monoamine oxidase, catechol O-methyltransferase, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid seemed to be neoplastic in origin, since electron microscopic studies failed to reveal the presence of any neuronal elements in this squamous epithelial cell carcinoma. Castration of rats significantly reduced the activity of tyrosine hydroxylase and the levels of tyrosine, dopamine, tryptophan, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in prostate tumors. The changes appeared to be androgen specific since reintroduction of testosterone restored several of these biochemical parameters virtually to control limits. Chemical sympathectomy induced by 6-hydroxydopamine failed to alter monoamine metabolism; however, the prostatic tumor grown in 6-hydroxydopamine-treated rats showed significantly (32%) less necrosis than those grown in normal animals.
 ...
PMID:Effect of testosterone and 6-hydroxydopamine treatment on the metabolism of catecholamine and 5-hydroxytryptamine in methylcholanthrene-induced prostate carcinoma of rats. 48 61

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.
 ...
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.
 ...
PMID:Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain. 97 62

We investigated the acute effects of a single i.c.v. injection of lithium chloride (LiCl) the neuroamine content of the rat mediobasal hypothalamus (MBH). The effects of lithium on amine synthesis and degradation enzymes were also studied in vitro. Noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were reduced 10 min after i.c.v. injection of 24 nmol of LiCl and returned to control values 30 min after the injection. Two nmol of LiCl reduced the concentration of DA (10 and 30 min after injection) and 5-HIAA (30 min after injection). LiCl (0.5-10 mM) inhibited tyrosine hydroxylase activity (catecholamine synthesis) in vitro in a concentration dependent manner. The i.c.v. administration of a high dose of LiCl reduced the content of neuroamines in the MBH. This might result from and inhibition of synthesis. A possible link between the observed changes and some reported side effects of lithium therapy is discussed.
 ...
PMID:Effects of i.c.v. lithium chloride administration on monoamine concentration in rat mediobasal hypothalamus. 135 89

Benzo[a]pyrene (BaP) is a product of incomplete fossil fuel combustion, a well-known pollutant, and a carcinogenic agent. In the present study male CD-1 mice received ip injections of 0, 5, 25, and 100 mg/kg body weight BaP twice a week for 3 weeks. Endogenous levels of brain biogenic amines and their selected metabolites, norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), vanillylmandelic acid, dihydroxyphenylacetic acid (DOPAC), homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high performance liquid chromatography and electrochemical detection. The brain regions studied were cortex, striatum, hypothalamus, midbrain, medulla oblongata, and cerebellum. BaP treatment increased the steady-state levels of NE, DA, and 5-HT in the hypothalamus and striatum. Increased levels of DA and 5-HT and their major metabolites DOPAC and 5-HIAA were noticed in the same region, an indication of increased metabolism of these amines. The increase in the 5-HT level in the cortex was not dose-related. Levels of NE and DA were significantly higher in the medulla oblongata. There was a concurrent increase in activities of tyrosine hydroxylase and tryptophan hydroxylase in several brain regions. The effect of BaP on Dopa-decarboxylase was not consistent. Monoamine oxidase was occasionally inhibited. Results indicate that exposure to BaP altered the steady-state levels of biogenic amines in various brain regions and these changes were consistent with the activities of metabolizing enzymes.
 ...
PMID:Effects of benzo[a]pyrene on steady-state levels of biogenic amines and metabolizing enzymes in mouse brain regions. 138 71

alpha-Methyl-p-tyrosine (alpha-MT), a competitive inhibitor of tyrosine hydroxylase, was used to block the synthesis of hypothalamic catecholamines in immature female rats of 14, 16 and 30 days of age and in castrated adults. The administration of alpha-MT (300 mg/kg body weight, free base) induced a significant decay in the hypothalamic content of norepinephrine (NE) and dopamine (DA) within the first 120 min. A second dose (150 mg/kg body weight), given 2 h after the first injection, did not further modify the low catecholamine levels observed 120 min after the first alpha-MT administration. The administration of 300 mg/kg body weight of alpha-MT induced a significant increase in LH concentrations in rats aged 14 and 16 days. On the contrary, after an alpha-MT injection, a significant LH decrease was observed in 30-day-old and in adult castrated rats. alpha-MT also increased FSH levels in prepubertal rats of 16 days of age, but no change occurred in 30-day-old and in adult rats. The administration of estrogen-progesterone (EP) to prepubertal rats of 16 days of age induced a significant decrease in serum LH levels as well as in the serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations in the anterior-preoptic hypothalamic area (AH-POA), but not in the medial basal hypothalamus. No modifications in the catecholamine content of these hypothalamic areas were observed in this age group after EP administration. On the contrary, in 30-day-old rats, EP induced a significant LH release as well as an increase in AH-POA concentrations of 5-HT, 5-HIAA and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Sexual maturation modifies the catecholaminergic control of gonadotrophin secretion and the effect of ovarian hormones on hypothalamic neurotransmitters in female rats. 170 90

The levels of serotonin (5-HT), 5 hydroxyindoleacetic acid (5-HIAA), dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), and tyrosine hydroxylase (TH) activity were measured in the focus (spiking) and nonfocus (nonspiking) regions of the temporal neocortex of 20 patients with intractable complex partial seizures. The levels of 5-HT, DA, 5-HIAA, and HVA were higher in the focus when compared to the nonfocus. Values for NE and TH activity were not different when focus and nonfocus were compared. The ratios of metabolite to precursor for 5-HT and DA were not significantly different between the focus and the nonfocus, suggesting that the changes observed were the result of a modification in the synthesis and release of these amines. Such changes in the epileptic focus could be caused by altered transsynaptic regulatory processes, which occur as a result of neuronal loss, gliosis, or neuronal sprouting.
 ...
PMID:Levels of biogenic amines, their metabolites, and tyrosine hydroxylase activity in the human epileptic temporal cortex. 196 84

Ipsapirone, a new anxiolytic drug with a high affinity to 5-HT1A receptors, given in a dose of 10 mg/kg ip markedly accelerated noradrenaline disappearance after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (250 mg/kg ip) in the cortex, hippocampus and hypothalamus of male Wistar rats. It also increased disappearance of dopamine and the level of 3,4-dihydroxyphenylacetic acid and homovanillic acid in the striatum. At the same time, the level of 5-hydroxyindoleacetic acid was decreased in the cortex, striatum, hypothalamus, but not changed in the hippocampus. 8-OH-DPAT, a selective agonist of 5-HT1A receptors, used in a dose of 5 mg/kg sc was less effective, having accelerated noradrenaline disappearance in the cortex and hypothalamus, and having increased only the level of homovanillic acid in the striatum. The effect of ipsapirone on catecholamine turnover might be secondary in relation to inhibition of the serotonin neurons. A direct interaction between ipsapirone and its metabolite 1-PP with alpha 1- and alpha 2-adrenoceptors is very likely, too.
 ...
PMID:Ipsapirone, a new anxiolytic drug, stimulates catecholamine turnover in various regions of the rat brain. 198 Mar 61


1 2 3 4 5 6 7 Next >>