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 presence of enzymes (tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H)) and enzymatic activities (monoamino oxidase, (MAO)) related to catecholamine synthesis and degradation have been investigated in cervical, thoracic and lumbar dorsal root ganglia (DRG) of adult male rats using immunohistochemical and enzyme histochemical techniques, respectively. A small population (between 2-4%) of TH-like immunoreactive and MAO positive neurons was found. They were small in diameter (18 +/- 2 microns), predominate in lumbar DRG and did not display D beta H-like immunoreactivity. These sensory neurons which are likely catecholaminergic were insensitive to systemic administration of capsaicin and 6-hydroxydopamine. Colchicine administration caused an increase of TH-like immunoreactivity and MAO activity. Pargyline produced an increase in TH-like immunoreactivity and the disappearance of MAO activity. The possible dopaminergic nature of the subpopulation of DRG sensory neurons investigated in the present study is discussed.
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PMID:Presence of catecholamine-related enzymes in a subpopulation of primary sensory neurons in dorsal root ganglia of the rat. 168 49

Although the golden hamster is widely used for studies on aggression, there have been no previous investigations of the role of biogenic amines in this species. Like the mouse, isolated male hamsters are highly aggressive towards a conspecific while grouped males are relatively unaggressive. Isolated males exhibited no differences in levels of midbrain or hypothalamic serotonin (5HT), 5-hydroxyindole acetic acid (5HIAA) or norepinephrine (NE) compared with grouped males. Nor were there differences in the percentage changes in 5HT or 5HIAA following monoamine oxidase inhibition by pargyline, nor in the percentage fall in hypothalamic NE after tyrosine hydroxylase inhibition by alpha-methyl-p-tyrosine (AMPT); midbrain NE in isolates (unlike grouped males) did not decline after AMPT administration. The percentage changes in 5HT after pargyline administration were unaffected by fighting, but the expected percentage fall in hypothalamic 5HIAA did not occur in males (either grouped or isolated) taking part in an aggressive interaction; this may be an indication of increased 5HT turnover. The percentage change in NE after AMPT administration was unaffected by fighting. Pargyline administration (70 mg/kg IP) reduced the aggressive response of isolated male hamsters to an intruder while AMPT (200 mg/kg IP) had no significant effect.
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PMID:The effects of isolation, grouping and aggressive interactions on indole- and catecholamine levels and apparent turnover in the hypothalamus and midbrain of the male golden hamster. 241 93

The kinetics of monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), in cisternal CSF were determined after monoamine oxidase (MAO) inhibition (pargyline, 100 mg/kg) and tyrosine hydroxylase inhibition (alpha-methyl-p-tyrosine, alpha-MPT, 250 mg/kg) in awake rats. In addition, the possibility of a peripheral contribution to CSF MHPG levels was investigated by infusing large amounts of the metabolite into vena jugularis. Pargyline induced an exponential decrease of CSF MHPG, 5-HIAA and HVA, with respective half-lives of 51, 86 and 46 min. alpha-MPT caused a slower decline of MHPG and HVA, while 5-HIAA was unaffected. Results from the MHPG-infusion experiments indicate minor peripheral contribution to CSF MHPG levels in acute pharmacological studies. The present paper gives further support for the validity of our new animal model in detecting acute changes in central monoaminergic activity.
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PMID:Monoamine metabolite levels in rat CSF: kinetic studies. 244 6

Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c., twice), with pargyline alone, or were uninjected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4-dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine beta-hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)-A and MAO-B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the nigrostriatal system, the dogs exhibited only a transient hypokinesia lasting 1-2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1-methyl-4-phenylpyridinium, selectivity in aminergic terminals.
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PMID:Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the dog: effect of pargyline pretreatment. 256 5

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its main metabolite 1-methyl-4-phenylpyridinium ion (MPP+) on the peripheral catecholaminergic system of the rat were investigated. MPTP and MPP+ injections (20 mg/kg i.p.) caused a marked acute depletion of heart noradrenaline, up to 75% twelve hours after the administration, and a decrease of adrenal gland adrenaline. The time-course of the effect of MPTP and MPP+ is reported, together with a decrease in the tyrosine hydroxylase activity after MPTP treatment, more evident in the adrenal glands. Pargyline (50 mg/kg i.p.) is not able to prevent such a neurotoxic peripheral effect.
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PMID:Acute peripheral catecholaminergic changes in rat after MPTP and MPP+ treatment. 257 Apr 48

The changes of free 3-methoxy-4-hydroxyphenylglycol (MHPG) in cerebrospinal fluid (CSF) were compared with the corresponding alterations of free and conjugated MHPG in rat brain tissue after various pharmacological treatments modifying noradrenergic neurotransmission. In addition, the effects of the drug treatments on the concentration of noradrenaline (NA) in brain were determined. alpha-Methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase) induced decreases in free and conjugated MHPG in CSF and brain; the free species appeared to decline more rapidly. Reserpine caused similar biphasic changes in free MHPG in CSF and brain but the rapid and transient initial increase in MHPG-SO4 was very weak. Pargyline (monoamine oxidase inhibitor) induced a sharp decline in the concentration of free MHPG in brain and CSF while MHPG-SO4 in brain definitely decreased more slowly. Relatively similar time courses were seen for all three MHPG parameters after administration of MPV-1248 (alpha 2-antagonist) and clonidine (alpha 2-agonist) i.e., increases and decreases, respectively. The present results support the validity of monitoring drug-induced acute changes in central turnover of NA by repeated measurements of free MHPG levels in rat cisternal CSF.
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PMID:Comparison of free MHPG in rat cerebrospinal fluid with free and conjugated MHPG in brain tissue: effects of drugs modifying noradrenergic transmission. 287 2

Nucleus tractus solitarius (NTS) is a brainstem nucleus known to play an important role in baroreceptor mediated cardiovascular regulation. As part of our study of the role of monoamines in the function of NTS, we have characterized pharmacologically the in vivo electrochemical signal recorded from the nucleus using carbon paste electrodes and linear sweep voltammetry with semiderivative signal processing in awake, freely moving rats. Two peaks were recorded by these techniques, one at 0.14 V and a second at 0.28 V. The tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine led to a significant reduction in the peak recorded at 0.14 V whereas it had no effect on the higher potential peak at 0.28 V. The dopamine-beta-hydroxylase inhibitor fusaric acid resulted in a large reduction in the 0.14 V peak and led to a 30% increase in the 0.28 V peak height. Pargyline, a monoamine oxidase inhibitor, did not change the low potential peak but did significantly reduce the 0.28 V peak. Tissue assays provided further support for the interpretation of in vivo electrochemical recordings. Norepinephrine concentration was reduced with fusaric acid. Tissue serotonin was not affected by any of the drugs while the 5-HIAA content was increased with fusaric acid and reduced with pargyline. These experimental findings lead to the conclusion that the first peak in the voltammogram most likely represents norepinephrine with a possible contribution by dopamine but not by DOPAC. The second peak appears to be 5-HIAA.
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PMID:Nucleus tractus solitarius: an evaluation by in vivo voltammetry. 288 6

Pargyline, an inhibitor of monoamine oxidase (MAO), prevented 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced inhibition of dihydroxyphenylalanine (DOPA) production by tyrosine hydroxylase (TH) system in rat striatal tissue slices. The result suggests that the metabolism of MPTP in rat striatal tissue slices by MAO is necessary for the expression of the inhibitory effect. 1-Methyl-4-phenylpyridinium ion (MPP+), the metabolic product of MPTP by MAO, also inhibited DOPA formation in rat striatal tissue slices. The concentration of MPP+ producing significant inhibition was lower than that of MPTP, and the maximal inhibition produced by MPP+ was greater than that caused by MPTP. Since MPP+ at a concentration of 10(-4) M had no effect on the activity of pure TH in vitro, the inhibition of DOPA formation in tissue slices induced by MPP+ may not be due to direct inhibition of TH. Although hydroxylated derivatives of MPTP were reported to inhibit dihydropteridine reductase in vitro at lower concentrations than MPTP, 1-methyl-4-(p-hydroxyphenyl)-1,2,3,6-tetrahydropyridine showed only weak inhibition for tyrosine hydroxylation in striatal tissue slices.
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PMID:Inhibition of tyrosine hydroxylation in rat striatal tissue slices by 1-methyl-4-phenylpyridinium ion. 392 90

1 Pargyline treatment, 1 h before (+)-amphetamine (1 mg/kg), reduced amphetamine-stimulated motor activity. This inhibition was reversed in animals pretreated with p-chlorophenylalanine (PCPA).2 Following treatment with PCPA or 5,6-dihydroxytryptamine (5,6-DHT), amphetamine-induced locomotor activity was significantly potentiated. The increased response to amphetamine in PCPA-treated rats was reversed in animals pretreated with 5-hydroxytryptophan.3 The inhibition of amphetamine-stimulated locomotor activity by treatment with 6-hydroxydopamine was not reversed by PCPA treatment.4 Stereotypies produced by amphetamine were not found to be altered by depletion of 5-hydroxytryptamine.5 Induction of adrenal tyrosine hydroxylase activity produced by chronic amphetamine administration was significantly potentiated by PCPA, emphasizing the involvement of a 5-hydroxytryptamine inhibitory system in more than one action of amphetamine.
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PMID:Evidence for involvement of 5-hydroxytryptamine in the actions of amphetamine. 415 93

After acute administration of the monoamine oxidase inhibitor clorgyline there is a reduction of aromatic L-amino acid decarboxylase and tyrosine hydroxylase activity in the mouse striatum. Similar responses were seen after administering the non-selective monoamine oxidase inhibitor pargyline and high, but not low, doses of the selective monoamine oxidase-B inhibitor deprenyl. Changes of tyrosine hydroxylase activity were observed only when subsaturated concentrations of the pteridine cofactor were used for the assay. The monoamine oxidase inhibitors altered the abundance of aromatic L-amino acid decarboxylase and tyrosine hydroxylase mRNA in the midbrain. Pargyline and high doses of deprenyl increased, aromatic L-amino acid decarboxylase mRNA, while clorgyline initially decreased and then increased it. All three compounds caused an early decrease of tyrosine hydroxylase mRNA. The acidic metabolites of dopamine appeared most affected by pargyline and clorgyline, supporting the notion that deamination of striatal dopamine in rodents is primarily by monoamine oxidase-A. Our results suggest, that striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase are apparently modulated via different mechanisms in response to perturbation of dopamine metabolism.
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PMID:Modulation of tyrosine hydroxylase and aromatic L-amino acid decarboxylase after inhibiting monoamine oxidase-A. 895 18


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