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)

Tyrosine hydroxylase and dopamine (DA)-beta-hydroxylase activities in rat brain and heart after disulfiram (DS) or diethyldithiocarbamate (DDC) administration have been determined in vitro and in vivo. DS and DDC in vitro stronger inhibit DA-beta-hydroxylase than tyrosine hydroxylase activity. 50% inhibition of tyrosine hydroxylase activity needed about twice higher concentrations of DS and DDC than the same inhibition of DA-beta-hydroxylase. Inhibition of the above enzymes in the in vivo experiments was DS or DDC dose dependent.
Pol J Pharmacol Pharm
PMID:Effect of disulfiram and sodium diethyldithiocarbamate on tyrosine and dopamine-beta-hydroxylases activities in rat brain and heart. 23 95

The effect of acute and chronic treatment of rats with IPF C-45 on the following biochemical and pharmacological parameters was tested: catecholamine concentration in brain, heart and adrenals, 3H-noradrenaline uptake by cardiac muscle, the action on catecholamine synthesis following treatment with alpha-methyl-p-tyrosine, reactivity of cardiovascular system to catecholamines and isoproterenol-induced tachycardia. Given chronically, IPF C-45 does not affect noradrenaline uptake by the cardiac muscle. Both chronic and acute administration of the drug decelerates catecholamine biosynthesis by inhibition of tyrosine hydroxylase activity. It seems that the action of IPF C-45, a benzonaphthyridone derivative, affects catecholamine metabolism in a manner distinctly different from that of tricyclic antidepressant drugs.
Pol J Pharmacol Pharm
PMID:Biosynthesis of catecholamines, uptake of 3H-noradrenaline, and reactivity of cardiovascular system of the rat after chronic and acute treatment with a new antidepressant agent, IPF C-45. 85 79

Four patients with severe form of Parkinson's disease received transplantation of fetal dopaminergic cells into the caput of the caudate nucleus. The operation was done by an original method using a device designed specially for this purpose. In all cases the duration of the disease was 10 to 15 years, and the predominating signs were tremor, bradykinesia, and markedly pronounced side effects of the treatment (on-off syndrome and involuntary movements). One patients died 5 weeks after the operation. Autopsy demonstrated good survival of the transplanted cells with good integration with the brain of the recipient and traces of positive immunocytochemical reaction for tyrosine hydroxylase. In the other patients a significant clinical improvement was noted after the operation, with reduced intensity of parkinsonian symptomatology, shortening of the duration of the off phase, improved motor ability and reduced intensity of the involuntary movements. The longest follow-up was 24 months.
Neurol Neurochir Pol 1992
PMID:[Transplantation of fetal dopaminergic cells in Parkinson disease]. 140 86

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.
Pol J Pharmacol Pharm
PMID:Ipsapirone, a new anxiolytic drug, stimulates catecholamine turnover in various regions of the rat brain. 198 Mar 61

The evidence for alterations in the dopaminergic system in animals induced by repetitive antidepressant treatment is discussed. Drugs with dopamine (DA) antagonistic, uptake inhibiting or releasing properties can be expected to cause receptor super- or subsensitivity, resp. MAO inhibitors cause a sustained suppression of DA synthesis due to direct inhibition of tyrosine hydroxylase by elevated cytosolic DA. With desipramine iprindol, electroconvulsive shock and REM sleep deprivation, there is some evidence for a development of postsynaptic DA receptor supersensitivity; this might, however, be secondary to effects of these treatments on the noradrenergic system. Nevertheless, it could play a role in the therapeutic effects of antidepressant treatments, in view of the role which the mesolimbic DA system seems to play in reinforcement and reward processes. Subsensitivity of presynaptic DA receptors was reported by two research groups to be caused by a variety of antidepressant treatments on the basis of biochemical, behavioural and electrophysiological data. Others were unable to reproduce or corroborate these findings. Taking into account the information hitherto available, the evidence for the development of presynaptic DA receptor subsensitivity after antidepressant treatment is not considered convincing.
Pol J Pharmacol Pharm
PMID:Effects of chronic antidepressant treatment on pre- and post-synaptic dopaminergic mechanisms. A short review of the literature and some complementary experiments. 614 29

Non-fluorescent, double-labeling techniques were used in order to investigate whether NMDAR1 receptor subunits are localized on dopaminergic (i.e. tyrosine hydroxylase-positive) neurons of the rat substantia nigra, pars compacta. It has been found that NMDAR1 receptor subunits are highly abundant in the pars compacta neurons and their dendritic processes. It was also found that vast majority, if not all, of pars compacta neurons which are positive for the presence of NMDAR1 receptor subunits are dopaminergic ones. It is concluded that if NMDAR1 receptor subunits, an indispensable element of functional NMDA receptor ion channel complex, is co-assembled with other subunits of NMDA receptor ion channel complex, NMDA receptors might directly control the activity of dopaminergic neurons.
Pol J Pharmacol
PMID:Immunohistochemical evidence for localization of NMDAR1 receptor subunit on dopaminergic neurons of the rat substantia nigra, pars compacta. 1198 45

Using non-fluorescent immunocytochemical double-labelling procedure and specific antibodies visualizing GR (glucocorticoid receptors) and TH (tyrosine hydroxylase) we have been looking for the co-localization of both antigens in neurons of the rat ventral tegmental area and adjacent substantia nigra. This experimental direction has been inspired by the available data showing that alterations in the level of circulating glucocorticosteroids have distinct effects on the intensity of dopaminergic neurotransmission. Thus, it was of interest to find the anatomical background for the above interaction. It has been found that the rat ventral tegmental area and substantia nigra possess a relatively moderate number of cells with active GR, i.e. receptors which are condensed in the nuclei. Further, we found that dopaminergic neurons (TH-positive) of the ventral tegmental area and substantia nigra were not immunopositive for GR. This observation was in the sharp contrast to the results from the locus coeruleus, where the co-localization of GR with TH was a general rule. Above anatomical data indicate that glucocorticoid receptors influence the dopaminergic neurotransmission by an indirect mechanism, which possibly involves intermittent neurotransmitter.
Pol J Pharmacol
PMID:Search for the presence of glucocorticoid receptors in dopaminergic neurons of rat ventral tegmental area and substantia nigra. 1198 46

Expression of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and choline acetyltransferase (ChAT) was studied with immunohistochemistry, in situ hybridization, RT-PCR and immunoblotting in two populations of neurons of porcine inferior mesenteric ganglion (IMG) projecting to the uterine horn and uterine cervix after axotomy induced by partial or total uterus extirpation in sexually immature gilts. Uterus-projecting neurons of the IMG were identified by retrograde tracing with Fast Blue. Additionally, the distribution of ChAT-positive (ChAT+) and Met-enkephalin-positive (ME+) nerve fibers around uterus-projecting neurons was studied with immunohistochemistry. Immunohistochemistry detected that extirpation-induced axotomy reduced dramatically TH, but not DBH, expression in the uterus-projecting neurons, while the expression level of ChAT remained unchanged. Hybridization in situ performed with molecular probes for TH and ChAT confirmed these findings. RT-PCR did not detect any changes in the expression of TH and ChAT at mRNA level between control and hysterectomized animals. Immunoblotting did not detect significant changes in the expression of TH and DBH in IMG after partial or total extirpation. However, it detected that after total extirpation of the uterus a new form of ChAT with apparent lower molecular mass appears in the IMG of hysterectomized animals. It was found also that the number of ChAT+ and ME+ nerve fibers is lower around axotomy-affected neurons than around neurons in control gilts. The results presented here show clear axotomy-associated changes in the expression of TH, but not DBH and ChAT in the uterus-projecting neurons of the porcine IMG, as well as changes in the expression of ChAT and ME in the preganglionic nerve fibers.
Pol J Vet Sci 2003
PMID:Effect of total or partial uterus extirpation on uterus-projecting neurons in porcine inferior mesenteric ganglion. A. Changes in expression of transmitter-synthesizing enzymes--tyrosine hydroxylase, dopamine beta-hydroxylase and choline acetyltransferase. 1281 84

Recently we have shown that in vitro binding of the proximal part of the human tyrosine hydroxylase gene to the nuclear matrix is correlated with its transcriptional activity. The strongest binding potential was predicted by computing for the first intron sequence (Lenartowski & Goc, 2002, Neurosci Lett.; 330: 151-154). In this study a 16 kb fragment of the bovine genomic DNA containing the tyrosine hydroxylase gene was investigated for its affinity to the nuclear matrix. Only a 950 bp fragment encoding the distal part of the first intron, second exon and a few nucleotides of the second intron bound to the nuclear matrix. The binding was independent of the tissue-specific tyrosine hydroxylase gene activation. The fragment was subcloned and sequenced. Computer search pointed to one potential intronic matrix attachment region with two AP1-like sites embedded in the sequence. We conclude that even if the position of the matrix binding region is conserved among the tyrosine hydroxylase genes in mammals, its tissue specificity and/or function is not preserved or is achieved by different mechanisms.
Acta Biochim Pol 2003
PMID:The bovine tyrosine hydroxylase gene associates in vitro with the nuclear matrix by its first intron sequence. 1451 67

Several lines of evidence indicate that exposure to various types of stressors, or stress hormones may increase or induce sensitization to psychostimulants or enhance susceptibility of experimental animals to the effects of abusing substances. In order to find out what is a biological substrate of the above phenomenon, we investigate the impact of stress hormones on the dopaminergic neurotransmission. It is postulated, first, that corticosterone, an important stress hormone, regulates the dopaminergic neurotransmission at the level of dopamine D-1 receptors. Secondly, corticosterone may enhance the dopaminergic tone by the alterations in the synthesis of tyrosine hydroxylase, however, it is also conceivable that, alternatively, corticosterone may evoke translocation of that enzyme from the cell bodies of dopaminergic neurons to their terminals. Finally, arguments that dopamine D-1 receptors might regulate the release of corticosterone by activation of neurons in the paraventricular nucleus of hypothalamus are discussed.
Pol J Pharmacol
PMID:Role of glucocorticoids in the regulation of dopaminergic neurotransmission. 1470 61


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