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)

Although the antiparkinsonian activity of 1-prolyl-l-leucyl-glycine amide (PLG=MIF-I) has been previously observed in several clinical trials, little is known of the mechanism of action of this tripeptide on the brain. Our study demonstrated potentiation of the action of apomorphine by PLG on the rotational behavior of mature rats which received unilateral 6-OHDA (16 microgram) lesions of the striatum as neonates. No change in tyrosine hydroxylase or dopa decarboxylase activities in rat striatal homogenates was found after addition of PLG (10(-8-10(-3) M). The results suggest that PLG modifies the dopamine receptor, making it more responsive to stimulation by the agonistic agent apomorphine and perhaps by the natural neurotransmitter dopamine.
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PMID:Potentiation of apomorphine action in rats by l-prolyl-l-leucyl-glycine amide. 3 Sep 81

The uterine adrenergic transmitter is in many animal species dramatically reduced during pregnancy, probably leading to a functional denervation near term. In order to clarify whether similar changes also occur in the human uterus, the adrenergic innervation of the isthmic myometrium during nonpregnant and pregnant conditions was analyzed by fluorescence histochemistry for demonstration of adrenergic nerves, and by quantitative measurements of norepinephrine and its synthesizing enzymes, tyrosine hydroxylase and dopa decarboxylase. At term pregnancy all fluorescent adrenergic nerves in the myometrium had disappeared, and the norepinephrine concentration had been reduced to almost zero. Parallel to this the activities of tyrosine hydroxylase and dopa decarboxylase were markedly reduced. By contrast, the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, was unchanged, indicating that the adrenergic system was selectively affected. The results confirm that the adrenergic nerves in the human uterus, like those in uterine horns of laboratory animals, undergo fundamental changes in the course of pregnancy. This probably reflects entirely different conditions for a sympathetic influence on the myometrium during the last two trimesters of pregnancy compared to the non-pregnant situation.
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PMID:Adrenergic innervation of the human uterus. Disappearance of the transmitter and transmitter-forming enzymes during pregnancy. 3 68

In an attempt to determine the mechanism by which the tripeptide l-prolyl-l-leucyl-glycine amide (PLG, MIF-I) exerts its antiparkinsonian effect, the action of this substance on various postsynaptic components of striatal dopaminergic nerves was studied. It was shown that injection of rats with MIF-I (1 mg/kg, IPX5, 24 hr intervals) did not alter tyrosine hydroxylase, dopa decarboxylase, choline acetyltransferase and glutamic acid decarboxylase activities in the striatum under the conditions tested. The activities of adenylate cyclase, dopamine-stimulated adenylate cyclase, and guanylate cyclase were not altered in vitro by various concentrations of MIF-I (0.1 to 1000 micrometer), although VIP and neurotensin had some effect. Also the rate of uptake of 3H-dopamine by rat striatal synaptosomes was unchanged, as was the binding of 3H-dopamine and 3H-spiperone to beef caudate membranes. This series of studies indicates that MIF-I does not act directly on the striatal dopamine postsynaptic receptor under the conditions tested, although it is possible that MIF-I could act indirectly at this or another site in vivo by releasing or activating some other factor.
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PMID:MIF-I and postsynaptic receptor sites for dopamine. 3 65

The cellular localization of the enzymes tyrosine hydroxylase (TH), aromatic amino-acid decarboxylase (or dopa decarboxylase, DDC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of adult rats and rat fetuses (14th, 17th, 18th, 19th and 21st day) was examined. In the prenatal stages the medullary blastema and an adjacent part of the primitive sympathetic trunk were also investigated. Tissues were fixed in ice-cold 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.2). Cryostat sections (10 micron in thickness) were stained by the indirect immunofluorescence technique. Rabbit antibodies to TH (isolated from human pheochromocytoma), DDC, DBH and PNMT (the latter three isolated from bovine adrenal medulla) were used. Sections incubated with serum of non-immunized rabbits were used as controls. In the adult adrenal medulla, two cell types can be distinguished. One cell type contains only TH, DDC and DBH. The other cell type contains PNMT in addition. It is concluded that these cells correspond to the noradrenaline-(NA-) and adrenaline- (A-)storing cells respectively. In all prenatal stages TH, DDC and DBH are found in the primitive sympathetic trunk, in the medullary blastema, and in the medullary cells which have migrated into the cortical "anlage". PNMT is observed for the first time on the 18th day. Moreover, PNMT could only be demonstrated inside the adrenal gland. From these observations it is concluded that the capacity to synthesize NA is developed even before the "medullary" cells have reached the cortical "anlage". On the contrary, the capacity to synthesize A seems to be acquired only after this contact is established. The hypothesis is put forward that this phenomenon might indicate the induction of PNMT by glucocorticoids secreted by the fetal cortex.
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PMID:Appearance of tyrosine hydroxylase, aromatic amino-acid decarboxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase during the ontogenesis of the adrenal medulla: an immunohistochemical study in the rat. 4 Jul

The clinical, pathological, and neurochemical characteristics of a newly recognized inherited neurological disorder are reported. Lethargy and mental depression are early symptoms, followed by mild parkinsonism and progressive weight loss. Failure of automatic respiratory control develops and may result in sudden death. Advanced degeneration of the substantia nigra, cell loss and gliosis of the basal ganglia, and focal gliosis in the medulla are seen on pathological study. Degeneration of the nigrostriatal dopaminergic system is evidenced by low levels of tyrosine hydroxylase, dopamine, homovanillic acid, and L-dopa decarboxylase in postmortem brain samples. Taurine concentrations in fasting plasma and CSF are somewhat depressed; brain contents of taurine are within normal limits.
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PMID:Familial fatal Parkinsonism with alveolar hypoventilation and mental depression. 4 4

The central nervous system of the mollusc Helix pomatia, like that of other molluscs, contains a very high level of dopamine. However, noradrenaline is weakly represented. These characteristics apply to the peripheral nervous system and more particularly to the heart. The study of the phenomena taking part in the synthesis and inactivation of catecholamines shows that these processes are not different in vertebrates and molluscs. Thus, in the particular case of Helix pomatia the synthesis of catecholamines is carried out by tyrosine hydroxylase, aromatic amino acid decarboxylase and dopamine-beta-hydroxylase. These enzymes are not only active in the ganglia and nerves, but also in the peripheral nervous system. The monoamines are associated with granules. The synthesized enzymes in the pericarya migrate due to the axonal flow and accumulate in the intracardiac nerve endings. In Helix pomatia, the enzymes participate actively in the local synthesis of catecholamines using the precursors tyrosine and DOPA. We have little information on the uptake of dopamine by nervous structures, but it would seem that this phenomenon seems to play an active role in the synaptic inactivation of dopamine. The glial elements also play a part in uptake and inactivation. In most species the nervous system has very little monoamine oxidase, and there is even less in the heart. The enzymic activity depends on substrates and is more active with dopamine than with 5-hydroxytryptamine. The exact localization of monoamine oxidase in the tissues is unknown. However, we believe that it plays a part in the neuronal regulation of dopamine levels and in its synaptic inactivation. The same applies for catechol O-methyltransferase.
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PMID:[The monoamines in molluscs. I. Catecholamines: biosynthesis, disposition and inactivation (author's transl)]. 4 29

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.
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PMID:Possible changes in striatal and limbic cholinergic systems in schizophrenia. 4 82

At various time points following acute and chronic administration of morphine to rats, dopamine transmitter metabolism and neuronal activity were determined. Following acute injection of morphine (20 mg/kg intraperitoneally), dopamine cell firing rates increased slowly and steadily. This slow increase was accompanied by a similar slow increase in the accumulation of the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC). Apparent in vivo tyrosine hydroxylase activity, measured by dopa accumulation following inhibition of dopa decarboxylase, also increased. In chronically treated animals the average firing rate of dopamine cells was measured two hours after the last injection of morphine. The distribution of dopamine cell firing rates was significantly higher than in controls. DOPAC levels and in vivo tyrosine hydroxylase activity were also increased at this time. When morphine (100 mg/kg intraperitoneally) was administered to chronically treated animals 12 hours after the last injection a slow increase of firing rates was observed similar to that seen in naive animals after an acute morphine injection. In chronically morphine treated animals naloxone caused a rapid dose-dependent decrease in firing rates and DOPAC levels. In vivo tyrosine hydroxylase activity was not changed.
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PMID:Dopaminergic neurons: effect of acute and chronic morphine administration on single cell activity and transmitter metabolism. 20 64

In the present study a series of 3-alkenyl-alpha-methyltyrosines and their corresponding 3-alkyl-and dihydrobenzofuran analogs was synthesized for potential tyrosine hydroxylase (TH) inhibitory activity. The appropriately substituted hydantoins IIIa and IIIb, which were prepared from the corresponding allyloxybenzylhydantoins IIa and IIb through Claisen rearrangement, served as intermediates for the synthesis of these amino acids. TH inhibition was reduced upon either saturation of the double bond in the side chain or cyclization to form the dihydrobenzofuran analogs. Formation of the epoxide had a similar effect. The inhibitory activity of these compounds against aromatic amino acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) was also investigated. Unsaturation, in both cases, decreases the inhibitory activity; however, the presence of a free phenolic group appears to be essential for AACD inhibitory activity.
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PMID:Aromatic amino acid hydroxylase inhibitors. 4. 3-Substituted alpha-methyltyrosines. 23 13

Postmortem changes in the activities of tyrosine hydroxylase, dopa decarboxylase, and dopamine-beta-hydroxylase were examined in various areas of rat brain. Tyrosine hydroxylase activity decreased in an exponential fashion with a half-time of two to four hours in caudate-putamen, substantia nigra, and locus ceruleus. Dopa decarboxylase activity remained within 20% of control values at five hours in these areas, but then decreased precipitously. Dopamine-beta-hydroxylase activity remained within 20% of control for at least 20 hours after death.
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PMID:Postmortem changes in brain catecholamine enzymes. 23 34


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