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)

Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.
Arch Gen Psychiatry 1977 Jan
PMID:Monoamine metabolism in human brain. 1 61

According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.
Arch Gen Psychiatry 1977 Jun
PMID:Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine. 1 74

Enzymes concerned with neurotransmitter metabolism were measured postmortem in 50 regions from the brains of 11 chronic schizophrenics, 2 patients with senile dementia, 1 depressive, and 18 controls. Enzymes studied were tyrosine hydroxylase, dopa decarboxylase, glutamic decarboxylase, choline acetyltransferase (CAT), and acetylcholinesterase. The schizophrenic group had high CAT activities in the hippocampus, caudate, putamen, and nucleus accumbens; the other patients from the same hospital did not. A compensatory response to long- or short-term drug usage is considered, but correlations are hard to establish in the group studied. An alternative hypothesis proposes that the high levels are a compensatory response to defective cholinergic receptors in the affected areas. On this hypothesis, and by analogy with chorea, dopaminergic antagonists would act in schizophrenia by helping to reestablish cholinergic-dopaminergic balance.
Arch Gen Psychiatry 1977 Nov
PMID:Possible changes in striatal and limbic cholinergic systems in schizophrenia. 4 82

Brain serotonin and dopamine (DA) turnovers in the female rainbow trout were studied at the beginning of the vitellogenesis and related to blood estradiol (E2) levels; pituitary and plasma gonadotropin (GtH) were also assayed. Ovariectomy did not modify brain aminergic turnover. E2 replacement on ovariectomized fish increased hypothalamic DA turnover (increased DA and increased DA metabolites). E2 stimulated GtH synthesis (positive feedback) but did not enhance GtH release; hypothalamic E2-mediated aminergic inhibition upon release was suspected. Individual relations between blood E2 levels and catecholaminergic neurotransmitters were determined. A linear positive correlation (r = 0.82) was found for the hypothalamus, but not for the pituitary, the preoptic area, or the telencephalon. These data suggest that an activation of hypothalamic tyrosine hydroxylase (the limiting step of catecholamines synthesis) by E2 could develop as vitellogenesis proceeds.
Gen Comp Endocrinol 1992 Nov
PMID:Effects of estradiol on brain aminergic turnover of the female rainbow trout (Oncorhynchus mykiss) at the beginning of vitellogenesis. 128 81

In the cerebrospinal fluid of the patients with Parkinson's disease treated with L-DOPA, L-3-O-methyldopa was the major metabolite of administered L-DOPA. Using a dopaminergic cell model, clonal rat phenochromocytoma PC 12h cells, and by microdialysis of the rat striatum it was proved that L-3-O-methyldopa was taken up into monoamine neurons by transport system specific for aromatic L-amino acids and inhibited transport of L-DOPA and other amino acids competitively. L-3-O-Methyldopa depleted allosteric regulation of the biopterin cofactor on activity of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. Depletion of the allostery may perturb the buffer action of endogenous L-DOPA synthesis that stabilizes dopamine level in the brain. By these mechanisms L-3-O-methyldopa may reduce clinical effectiveness of administered L-DOPA and be involved in wearing-off phenomenon. L-DOPA inhibited the activity of tryptophan hydroxylase and thus serotonin synthesis, which may be related to psychiatric side-effects in the patients under L-DOPA therapy.
J Neural Transm Gen Sect 1992
PMID:The mechanism of perturbation in monoamine metabolism by L-dopa therapy: in vivo and in vitro studies. 136 50

In this work, we have studied the time-course of the effects of pharmacological administration of ovarian steroids on tyrosine hydroxylase (TH) activity in the limbic forebrain of ovariectomized rats. Administration of estradiol produced a late decrease in TH activity. This effect was found 24 hours after the last steroid injection, disappearing at 32 hours. It was antagonized by progesterone, since a single injection of this steroid to estradiol-pretreated rats reversed to control values the estradiol-induced decrease. Nevertheless, the administration of progesterone after estradiol treatment caused a short-time decrease in the limbic activity of TH, which was observed 4 hours after the last steroid injection, disappearing subsequently. On the other hand, the administration of progesterone alone produced a biphasic effect, with a reduction at 24 hours, followed by an increase at 32 hours. These effects were only observed in the animals non-treated with estradiol, disappearing with a previous treatment with estrogens. Hence, it can be concluded that both ovarian steroids may affect the limbic TH activity. Thus, estradiol produced a late inhibitory effect on the activity of this enzyme, which was antagonized by progesterone. Administration of the last one to estradiol-treated rats produced a short-time inhibitory effect, whereas its administration to non-treated rats produced a late biphasic effect (inhibition followed by stimulation), which was not observed in estradiol-treated rats.
J Neural Transm Gen Sect 1991
PMID:Time-dependent effects of ovarian steroids on tyrosine hydroxylase activity in the limbic forebrain of female rats. 167 46

Enzyme activities associated with the neurotransmitter pathways in nerve growth factor-treated, 139A scrapie strain-infected PC12 cells were examined. Since these cells show no morphological alterations during the time of agent replication, any scrapie-induced effects would have to be associated with non-vital cellular functions. When compared to controls, infection with the 139A scrapie strain resulted in decreased activity of the cholinergic pathway-related enzymes, choline acetyltransferase and acetylcholinesterase. However, the adrenergic pathway was unaffected by scrapie infection as evidenced by unaltered tyrosine hydroxylase activity, the putative rate-limiting enzyme in the synthesis of catecholamines. The effects of the 139A scrapie strain on the cholinergic system appeared to be dose-dependent and were first detected prior to the detection of scrapie agent replication in these cells. Furthermore, the altered enzymic activities observed were not the result of contaminating material in the scrapie brain homogenate because similar results were obtained when partially purified scrapie preparations were used as the inoculum. These scrapie agent-induced alterations in specific neuronal properties suggest a mechanism for the clinical manifestations observed in scrapie and perhaps other related central nervous system disorders.
J Gen Virol 1991 Jun
PMID:Alterations in neurotransmitter-related enzyme activity in scrapie-infected PC12 cells. 167 47

In this work, we have studied the changes in the functional state of nigrostriatal (NSDA) and mesolimbic (MLDA) dopaminergic neurons during the estrous cycle of the female rat. The activity of tyrosine hydroxylase (TH), the turnover rate (Kt) after inhibition of dopamine (DA) synthesis and the ratio between the contents of this amine and its metabolite, L-3,4 dihydroxyphenylacetic acid (DOPAC), were used as indices of neuronal activity. The neuronal activity of NSDA neurons rose during estrous and declined during proestrous, as reflected by the values of Kt and DOPAC/DA ratio measured during both phases. Interestingly, the course of variations in striatal TH activity was similar, although retarded in relation to the changes in neuronal activity. Thus, TH activity was high during diestrous, whereas it was low during estrous. The activity of MLDA neurons was reduced during proestrous. This can be concluded from the decreased Kt and DOPAC/DA ratio measured in this phase and it was accompanied by a low TH activity. Thereupon, both Kt and TH activity increased during estrous. These results indicate the existence of physiological changes in the functional state of both dopaminergic systems during the ovarian cycle, which are partially different for each neuronal pathway. This supports the existence of a specific regulation, and not indiscriminate effects, by the hormones involved in this cycle, mainly estradiol and progesterone.
J Neural Transm Gen Sect 1991
PMID:Nigrostriatal and mesolimbic dopaminergic activities were modified throughout the ovarian cycle of female rats. 168 24

Levels of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (serotonin, 5-HT) and their metabolites, and the activities of tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH) and monoamine oxidase A and B (MAO-A and MAO-B) have been determined in the rat posterior thalamus after enucleation during postnatal development. DA and 5-HT turnover rate have been measured as 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) accumulation rates after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015). The major changes were an increase in noradrenergic and serotoninergic metabolism in enucleated animals compared with control animals. A decrease of the MAO-A to MAO-B ratio during postnatal development was found.
J Neural Transm Gen Sect 1991
PMID:Effects of neonatal bilateral eye enucleation on postnatal development of the monoamines in posterior thalamus of the rat. 168 25

The activities of tyrosine hydroxylase and tryptophan hydroxylase and contents of biopterin and neopterin were measured for the first time in various regions of human brain from a patient with anorexia nervosa (AN). In AN as compared with controls, tyrosine hydroxylase activity was markedly reduced in all brain regions analyzed, while tryptophan hydroxylase activity and biopterin content had a tendency to increase. Neopterin content did not change dramatically. The opposite changes of tyrosine hydroxylase and tryptophan hydroxylase suggest an imbalance between the activity of catecholaminergic neurons and that of serotonergic neurons, and may be related to pathogenesis of AN.
J Neural Transm Gen Sect 1990
PMID:Tyrosine hydroxylase, tryptophan hydroxylase, biopterin, and neopterin in the brain of anorexia nervosa. 196 83


1 2 3 4 5 6 7 8 Next >>