Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought to determine, in rat embryo, when and at what site in their migration cells derived from the neural crest differentiate into sympathetic neuroblasts. This has been accomplished by immunocytochemical detection, within the cells, of the enzymes catalyzing catecholamine biosynthesis-tyrosine hydroxylase [TH; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] dopamine-beta-hydroxylase [DBH; 3,4-dihydroxyphenylethylamine,ascorbate:oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1)]-and, as a marker of prospective adrenal medullary cells, the enzyme phenylethanolamine N-methyltransferase (PNMT; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28). TH and DBH, not detected in the neural crest, appear almost simultaneously in cells of the thoracic sympathetic ganglia in 11-day-old embryos, and in abdominal and lumbar ganglia 1-2 days later, thereby exhibiting a characteristic rostral-caudal gradient of differentiation. Cells stained for TH and DBH are seen in the gut wall from day 11 to day 14, but not thereafter. Cells stained for TH and DBH appear in the adrenal anlage at day 15. However, PNMT is not detected in the adrenal until day 17 of development, and is present only in the sympathoblasts in contact with the adrenal cortex. Treatment of pregnant rats with dexamethasone failed to accelerate the appearance of PNMT in the embryo or to initiate its expression in cells of other sympathetic organs. We conclude that neural crest cells express a noradrenergic phenotype only after leaving the neural crest and that these cells are labile with respect to their neurotransmitter and are capable of transformation in response to environmental stimuli.
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PMID:Appearance of catecholamine-synthesizing enzymes during development of rat sympathetic nervous system: possible role of tissue environment. 3 53

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

Nerve growth factor (NGF) is a protein essential for the development and maintenance of the peripheral sympathetic nervous system, causing responsive neurones to increase in size and to extend neurites. Biochemically, the selective induction of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase key enzymes in catecholamine biosynthesis is one of its most characteristic effects. Both the morphological and biochemical effects are modulated by glucocorticoids, suggesting a close relationship between specific effects of NGF and hormone action. NGF has been shown to induce an increase in adrenal cyclic AMP in intact but not in hypophysectomised rats, and so we have looked directly at the effect of systemic administration of NGF on the hypothalamo-pituitary-adrenal axis. We report here that NGF induced an enhanced secretion of adrenocorticotropin (ACTH) and a prolonged increase in plasma glucocorticoid concentration after intravenous (i.v.) injection. Such effects could have important implications for the biological activity of NGF.
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PMID:Stimulation of the pituitary-adrenocortical axis by nerve growth factor. 4 Nov 86

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

Chronic morphine administration in adult rats results in neurogenic secretion of adrenal catecholamines and compensatory increases in basal catecholamine levels, in activities of catecholamine biosynthetic enzymes and in the number of storage vesicles in the tissue. Perinatally addicted developing rats demonstrated changes completely different from those seen in adults; catecholamine levels and dopamine beta-hydroxylase activity were reduced compared to controlscsnnofinduction of tyrosine hydroxylase was observed. The time course of adrenomedullary maturation was delayed throuth the first 10-20 days of age, with reduced numbers of storage vesicles and larger proportions of partially filled vesicles. On exposure to morphine, continued until weaning, perinatally addicted rats did not display any of the changes in catecholamine synthesis or uptake seen in adult rats. The differences between adults and developing rats can be partly explained by the absence of functional innervation of the neonatal adrenal medulla.
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PMID:Sympatho-adrenal development in perinatally addicted rats. 24 Feb 52

Catecholamine storage was examined in cultures of the murine neuroblastoma cell line, N-TD6, using histofluorescence, electron microscopic, isotopic and radioautographic criteria. This line was originally derived from uncloned, C1300 tumor cells by selection in tyrosine deficient medium. N-TD6 cells possess both tyrosine hydroxylase (tyrosine-3-monooxygenase, EC 1.14.16.2) and dopamine beta-hydroxylase (dopamine beta-monooxygenase, EC 1.14.17.1) activities. When examined for paraformaldehyde-induced histofluorescence, a small percentage of cells in the population show intense catecholamine fluorescence, often localized within discrete regions of the cellular processes. Electron microscopic examination of these cells reveals both electron lucent vesicles and more frequent, electron dense granules, 50-70 nm and 100-300 nm in diameter, respectively. The distribution of these granules and vesicles varies, but they appear most numerous near the cell surface, along processes and within process endings. By labeling cells with [3H]dopamine and then allowing the cells to release unbound label in the presence of unlabeled dopamine, the localization of catecholamine stores was visualized by radioautographic techniques. While a variety of intracellular distribution of radioactivity were observed, the most prominent concentrations were found in the processes and their terminals; no labeled material was retained when reserpine was present during uptake. The topographic coincidence of granules, catecholamine fluorescence and [3H]dopamine retention in these neuroblastoma cells suggests that catecholamines are stored within these granules in a manner analogous to that observed in normal adrenergic neurons.
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PMID:Localized catecholamine storage associated with granules in murine neuroblastoma cells. 24 Apr 85

The endogenous levels of dopamine (DA) in the rat heart and submaxillary gland after a single, large dose of reserpine (10 mg/kg i.p.) were reduced to near zero within 1 h and were restored to normal within 48 h, while the noradrenaline (NA) levels reacted much more slowly. The data suggest that newly formed DA is rapidly taken up by the reserpinesensitive mechanism of the amine storage granules. The more rapid restoration of DA than of NA levels may be due to preferential release of newly formed NA by the nerve impulse. Electrical stimulation of the cervical sympathetic with 5 Hz for 30 min 4 h after the administration of reserpine increased the DA level of the submaxillary gland of the stimulated side, suggesting an increased tyrosine hydroxylase activity during stimulation, also in nerve terminals affected by reserpine. The use of an inhibitor of monoamine oxidase (pargyline) and/or an inhibitor of dopamine beta-hydroxylase (FLA-63) did not significantly alter the increase of DA following nerve stimulation, suggesting DA was protected by granular uptake. The stimulation-induced increase in DA was, however, much less in reserpine-treated than in normal animals, demonstrating the importance of the reserpine-sensitive uptake mechanisms for preserving newly formed DA.
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PMID:Recovery of dopamine in peripheral adrenergic nerves after reserpine treatment. 94 May 94

By screening of culture filtrates of fungi and streptomyces for activity in inhibit dopa decarboxylase the following isoflavone compounds were obtained: psi-tectorigenen (I), genistein (II), orobol (IV), 8-hydroxygenistein (V) and a new compound (III). III was elucidated to be 3', 4', 5, 7-tetrahydroxy-8methoxy isoflavone. Among these isoflavones, IV and III showed the strongest activity in inhibiting dopa decarboxylase. All these isoflavones also inhibited histidine decarboxylase and catechol-O-methyltrasnferase. Activities of these compounds to inhibit tyrosine hydroxylase and dopamine beta-hydroxylase were examined. Orobol which showed no or only slight inhibition of tyrosine hydroxylase and dopamine beta-hydroxylase exhibited a significant hypotensive effect on spontaneously hypertensive rats.
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PMID:Isolation of isoflavones inhibiting DOPA decarboxylase from fungi and streptomyces. 120 8

Reserpine (1 mg/kg s.c.) was administered to pregnant rats at different periods of gestation. Rats born to mothers who received reserpine on days 6, 5 and 4 or 4, 3 and 2 before delivery showed early postnatal adrenal catecholamine depletion, an effect which can be attributed to a direct action of the drug; however, at no time was induction of tyrosine hydroxylase or dopamine beta-hydroxylase observed. Administration of reserpine on days 9, 8 and 7 before delivery did not alter postnatal adrenal catecholamine levels in the offspring but produced permanent elevations in enzyme activities and vesicular amine uptake beginning at 10 days of age. Studies utilizing direct stimulation with nicotine indicated that the inherent responsiveness of the adrenal medulla itself was the same in control and reserpine-exposed pups. These data all suggest that sympathoadrenal tone has been permanently increased in the offspring of rats which have been exposed to reserpine early in gestation. In the brain, administration of reserpine on days 6, 5 and 4 before delivery resulted in a delay in early postnatal development of brain weight and synaptosomal uptake mechanisms, and at later stages subnormal tyrosine hydroxylase activities. When reserpine was given on days 9, 8 and 7 before delivery, only the deficiency in tyrosine hydroxylase was seen. These studies indicate that long-lasting changes in both peripheral and central nervous system catecholamine disposition can be produced by prenatal reserpine administration.
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PMID:Effects of prenatal reserpine administration on development of the rat adrenal medulla and central nervous system. 127 Dec 81

The transsynaptic induction of the monoamine transporter present on the membrane of chromaffin granules was studied in primary cultures of dissociated bovine adrenomedullary cells submitted to a chronic secretory stimulation. The amount of the vesicular monoamine transporter was assayed by binding of the specific ligand [3H]-dihydrotetrabenazine. After several days of incubation in the presence of high potassium, the concentration of [3H]-dihydrotetrabenazine binding sites was increased by a 1.5-2.5 factor. This increase was smaller in the presence of the cholinergic agonist carbachol. The long-term inductions of the vesicular monoamine transporter, of tyrosine hydroxylase, and of acetylcholinesterase were of similar magnitude. Under the same conditions, we found no variation in either the activities of other catecholamine biosynthetic enzymes (dopamine beta-hydroxylase and DOPA decarboxylase), or in metabolic enzymes such as lactate dehydrogenase and cytochrome c oxidase, and a decrease in the cellular content of chromogranin A and cytochrome b-561. The induction of the vesicular monoamine transporter was inhibited by the calcium channel antagonists, fluspirilene and nifedipine, and was increased by the agonist Bay K 8644. It was abolished by cycloheximide and actinomycin D. These results indicate that calcium entry into chromaffin cells increases the synthesis of the vesicular monoamine transporter, presumably by transcriptional activation. Elevation of intracellular cyclic AMP concentration or activation of protein kinase C also induced an increase in the expression of the vesicular monoamine transporter. Our results confirm that components of storage vesicle membranes are differentially regulated in response to secretory stimulation, as are several cytosolic or intravesicular soluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the chromaffin granule catecholamine transporter in cultured bovine adrenal medullary cells: stimulus-biosynthesis coupling. 127 22


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