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 metabolism of dopamine, norepinephrine and serotonin was studied in normoxic or hypobaric hypoxic rats, using HPLC with electrochemical detection. The changes in serotonin and its metabolite 5 hydroxy indolacetic acid (5 HIAA) levels in the hypoxic striatum and hypothalamus suggest an inhibition of 5 HIAA formation and a complex interaction between synthesis, release and uptake. Hypoxia caused a decrease of the striatal levels of homovanillic acid (HVA), dihydroxy 3-4 phenylacetic acid (DOPAC) [inhibition of tyrosine hydroxylase (TH) and monoamine oxidase (MAO)] and 3-methoxytyramine (3 MT) (inhibition of release). Striatal dopamine levels were increased, suggesting an increase in granular dopamine storage, with an impaired release. Hypothalamic levels of norepinephrine were decreased during hypoxia [(inhibition of TH, MAO, and dopamine beta-hydroxylase (DBH)].
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PMID:Dynamic characteristics of dopamine, norepinephrine and serotonin metabolism in axonal endings of the rat hypothalamus and striatum during hypoxia: a study using HPLC with electrochemical detection. 242 39

The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits and decreased concentrations of dopamine, homovanillic acid, and 3,4-dihydroxy-phenylacetic acid (DOPAC) and [3H]dopamine uptake in the caudate-putamen. There was an 80% reduction in tyrosine hydroxylase immunoreactive cells in substantia nigra. At 10 days following the start of MPTP administration, the activity of choline acetyltransferase in the thalamus and frontal cortex was unchanged compared with control animals. Similarly, specific [3H]QNB binding was unaltered. At 4-6 weeks following the start of MPTP treatment, choline acetyltransferase activity and [3H]QNB binding in the frontal cortex and thalamus remained unaffected. There was no evidence for cell loss in the nucleus basalis of Meynert or alteration in the intensity of staining for acetylcholinesterase. MPTP treatment of the common marmoset produces a nigrostriatal lesion. In contrast, MPTP did not alter cortical cholinergic function and was not neurotoxic to the cholinergic cells in the nucleus basalis of Meynert.
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PMID:Administration of MPTP to the common marmoset does not alter cortical cholinergic function. 314 64

Administration of the irreversible cholinesterase inhibitor isoflurophate (diisopropylfluorophosphate, DFP) before 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) enhanced the loss in tyrosine hydroxylase activity and dopamine and 3,4-dihydroxy-phenylacetic acid content in the striatum of mice in a dose-dependent manner. The effect of DFP on the MPTP-induced changes of dopaminergic markers was evident 30 days after initiating treatment, suggesting augmented neurotoxicity. Neurotoxicity was also enhanced by prior treatment with nicotine, carbachol or oxotremorine. We conclude that activation of either muscarinic or nicotinic receptors enhances the neurotoxicity of MPTP.
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PMID:Enhanced MPTP neurotoxicity after treatment with isoflurophate or cholinergic agonists. 791 17

Several neurotransmitters are implicated in the photoperiodic regulation of prolactin and luteinising hormone (LH) secretion in the ewe. This work investigated whether catecholamines, gamma-amino butyric acid (GABA), excitatory amino acids and serotonin diencephalic contents are affected by photoperiod and how such changes relate to the seasonal effects of photoperiod on LH and prolactin secretions. Moreover, to determine whether photoperiod can influence catecholamine biosynthesis, the activity of its rate limiting enzyme, tyrosine hydroxylase (TH) was also investigated. TH activity and the tissue content of the monoamines and their metabolites were measured in stalk-median eminence (SME), preoptic area (POA) and the mediobasal, mediodorsal and laterobasal aspects of the hypothalamus. Investigation of excitatory amino acids and GABA was limited to the POA and the SME. Ovariectomized ewes were initially maintained in long days (LD) for 70 days. Thereafter half the ewes remained exposed to long days and the other half were transferred onto short days (SD) for 63 to 66 days to induce a stimulation of LH secretion and an inhibition of prolactin secretion. In each photoperiodic regime, half the ewes were treated with a subcutaneous oestradiol implant (+E) and half were not (-E). As expected, short days induced a decrease in prolactin and an increase in pulsatile LH secretion. These neuroendocrine changes were associated with a decrease in the TH activity of the SME in both oestradiol treated and non treated animals (146.5 +/- 24.1, 167.6 +/- 26.5 U TH/g of tissue in LD-E and LD+E vs 83.5 +/- 12.4 and 95.0 +/- 30.2 U TH/g of tissue in SD-E and SD+E animals; P < or = 0.01). A similar and parallel short day-induced decrease was observed in the tissue content of dopamine and its metabolite, 3,4-dihydroxy-phenylacetic acid (SD level were 55% of LD levels, P < 0.05). In POA, a short day-induced decrease in dopamine (18%; P < or = 0.05) and GABA (16.4%; P < or = 0.05) content and an oestradiol-induced decrease in aspartate (15.6%; P < or = 0.05) content were found. This study provides the first report of a photoperiodic control of the synthesis activity of catecholaminergic neurones of the SME in the ewe. The photoperiod-induced changes in dopaminergic activity at the level of the SME were associated with changes in LH and prolactin secretion indicating that TH activity of dopaminergic neurones of the SME could be a critical component of the photoperiodic regulation of LH and/or prolactin secretion. In particular, this finding is in agreement with the hypothesis that photoperiod can control a dopaminergic pathway inhibitory of LH secretion and which ends in the median eminence.
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PMID:Photoperiodic modulation of monoamines and amino-acids involved in the control of prolactin and LH secretion in the ewe: evidence for a regulation of tyrosine hydroxylase activity. 880 77

The highly reactive nature of dopamine renders dopaminergic neurons vulnerable to oxidative damage. We recently demonstrated that loss-of-function mutations in the Drosophila gene Catecholamines up (Catsup) elevate dopamine pools but, paradoxically, also confer resistance to paraquat, an herbicide that induces oxidative stress-mediated toxicity in dopaminergic neurons. We now report a novel association of the membrane protein, Catsup, with GTP cyclohydrolase rate-limiting enzyme for tetrahydrobiopterin (BH(4)) biosynthesis and tyrosine hydroxylase, rate-limiting enzyme for dopamine biosynthesis, which requires BH(4) as a cofactor. Loss-of-function Catsup mutations cause dominant hyperactivation of both enzymes. Elevated dopamine levels in Catsup mutants coincide with several distinct characteristics, including hypermobility, minimal basal levels of 3,4-dihydroxy-phenylacetic acid, an oxidative metabolite of dopamine, and resistance to the vesicular monoamine transporter inhibitor, reserpine, suggesting that excess dopamine is synaptically active and that Catsup functions in the regulation of synaptic vesicle loading and release of dopamine. We conclude that Catsup regulates and links the dopamine synthesis and transport networks.
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PMID:Catecholamines up integrates dopamine synthesis and synaptic trafficking. 2198 68

Environmental heat stress is associated with physical stress responses, including changes in monoamines, protein expression, and neuronal circuits and damage to neurons in the brain. This study determined the effects of heat stress on the nigrostriatal dopaminergic system based on behavioral, histological, and neurochemical analyses. To evaluate behavioral changes after heat exposure, we subjected mice to the pole and open field tests. The data suggested that heat stress for 7 d significantly impaired movement. Then, we conducted a histological analysis using tyrosine hydroxylase (TH) immunoreactivity in the striatum and substantia nigra (SN). Heat stress induced a significant deficit in TH-positive fibers and cells after 14- and 21-d exposure, respectively. We also measured the striatal dopamine (DA), 4-hydroxy-3-methoxy-phenylacetic acid, and 3,4-dihydroxyphenylacetic acid levels. The data suggested that DA turnover rate increased with heat exposure in a time-dependent manner, resulting in the significant decrease of DA after 28 d. Moreover, the expression of heat shock protein 70 (HSP70) was increased in the mouse SN with up to 14-d heat exposure, but decreased after 21 d of the stress. And glucose-regulated protein 78 (GRP78) was gradually increased in the mouse SN with 28-d heat exposure. The caspase-3 activity was also increased after 14-d heat exposure. These findings are the first evidence that repeated heat stress impairs nigrostriatal dopaminergic neurons, motor function, and DA availability with changes of HSP70 and GRP78 expressions and caspase-3 activity in mice.
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PMID:Repeated heat exposure impairs nigrostriatal dopaminergic neurons in mice. 2384 35