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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)

A specific antiserum was used to compare phosphorylation of tyrosine hydroxylase (TH) (EC 1.14.16.2, tyrosine 3-monooxygenase) as regulated by elevated K+ and nerve growth factor (NGF) in cultured PC12 pheochromocytoma cells. Exposure of cultures to either elevated K+ or to NGF significantly enhanced the incorporation of [32P]orthophosphate into TH. The effect of elevated K+ was evident at 10 mM and was maximal by 40-80 mM. Increased phosphorylation of TH was detected at 0.1 nM (3 ng/ml) NGF and reached a maximal level by 0.3-1 nM (10-30 ng/ml) NGF. Elevated K+ showed a biphasic time course of action with one maximum of phosphorylation at about 30 sec of exposure and a second after about 10 min of exposure. In contrast, the NGF effect showed an initial lag of several minutes followed by a monophasic increase in phosphorylation to reach a plateau. Both treatments enhanced TH activity, but in each case the time courses of this did not strictly correlate with that of phosphorylation. The effect of elevated K+ on TH phosphorylation required the presence of extracellular Ca2+ and was suppressed by trifluoperazine (100 microM). N-(6-Aminohexyl)-5-(chloronaphthalene)-1-sulfonamide (W-7) (100 microM), a potent inhibitor of calmodulin activity, also blocked the enhancement of phosphorylation by elevated K+, whereas N-(6-aminohexyl)-1-(naphthalene)sulfonamide (W-5) (100 microM), a less potent analogue of W-7, did not. In contrast to these findings, the increase in TH phosphorylation brought about by NGF did not require extracellular Ca2+, and was only slightly affected by trifluoperazine or W-7. When TH phosphorylated under various conditions (control medium, elevated K+, NGF) was subjected to peptide mapping after exposure to Staphylococcus aureus protease V8, multiple phosphorylated peptides were observed. Elevated K+ and NGF each produced increases in labeling of each of the peptides. However, the relative degree of labeling of different peptides was distinct for each condition. These data suggest that elevated K+ and NGF bring about rapid enhancement of the phosphorylation of TH by means of different mechanisms.
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PMID:Regulation of tyrosine hydroxylase phosphorylation in PC12 pheochromocytoma cells by elevated K+ and nerve growth factor. Evidence for different mechanisms of action. 286 75

In cat retina, antisera directed against tyrosine hydroxylase (tyrosine 3-monooxygenase; EC 1.14.16.2) labeled three morphologically distinct classes of neurons; amacrine cells, displaced amacrine cells, and interplexiform cells. These three cell populations differed not only in their morphologies but also in their numbers, densities, and retinal distributions. Insofar as tyrosine hydroxylase-like immunoreactivity is associated with dopaminergic neurons, these observations suggest that the dopamine system in cat retina is morphologically heterogeneous and that the cat retina contains functional subdivisions based on the different distributions of specific cell populations.
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PMID:Morphology and distribution of tyrosine hydroxylase-like immunoreactive neurons in the cat retina. 286 20

The PC12 cell line derived from a rat adrenal medullary tumor is known to synthesize dopamine and to release it in response to cholinergic agonists or depolarizing agents. In this report, we have studied the relationship between dopamine biosynthesis and its stimulus-induced secretion in PC12 cells as a function of cell growth. The endogenous dopamine content was found to depend on cell growth, and reached a maximum in the stationary phase. This increase was associated both with an increase in the specific activity of tyrosine 3-monooxygenase, and with an increase of DOPA-decarboxylase in the cells. On the other hand, the maximal release of dopamine occurred in the late exponential phase before the endogenous dopamine was maximally synthesized in the cells. Moreover, the uptake of 45Ca2+ stimulated with either carbamylcholine or high K+ was also regulated by cell division: the maximal uptake took place in the same period of culture in which the maximal release of dopamine was observed. Thus, this report offers new evidence that the biosynthesis and secretion of dopamine are separately regulated in PC12 cells.
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PMID:Relationship between dopamine content and its secretion in PC12 cells as a function of cell growth. 286 58

Catecholamine biosynthesis and its stimulus-evoked release in PC12 pheochromocytoma cells were studied as a function of cell cycle by means of HPLC with electrochemical detection. We found that 3,4-dihydroxyphenylethylamine (dopamine) levels in PC12 cells remained constant throughout the period of cell cycle. In contrast, the noradrenaline content was dependent on the cell cycle: it increased during the S + G2 phase followed by a decrease in the M phase. These results were confirmed further by measuring the activities catalyzing the catecholamine biosynthesis. Thus, activities of tyrosine 3-monooxygenase and 3,4-dihydroxyphenylalanine decarboxylase were independent of the cell cycle, whereas both soluble and membrane-bound dopamine beta-monooxygenase activities were modulated during the cell cycle. On the other hand, release of the catecholamines stimulated with 50 mM KCl increased in the G1 phase, reached a maximum in the late G1, and then gradually decreased in later periods. We also found that carbamylcholine-induced release of the catecholamines occurred maximally in the early S + G2 phase followed by a decrease during the M phase. Cell cycle dependence of the catecholamine release was in good agreement with that of 45Ca2+ uptake. Thus, this study provides evidence that the catecholamine biosynthesis and its release in PC12 cells are modulated during the period of cell cycle.
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PMID:Cell cycle-dependent modulation of biosynthesis and stimulus-evoked release of catecholamines in PC12 pheochromocytoma cells. 287 Jan 33

Tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and phenylethanolamine N-methyltransferase, EC 2.1.1.28) are involved in catecholamine biosynthesis and are considered soluble proteins. However, they may actually be localized on the surface of the chromaffin granule. We have used the detergent digitonin to permeabilize the plasma membrane of cultured adrenal chromaffin cells to investigate the subcellular localization of TyrOHase and PMTase. A digitonin titration of the release of proteins and catecholamines revealed the existence of at least three subcellular compartments that are distinguished by their digitonin sensitivity: (i) soluble proteins, which were released upon treatment of the cells with low digitonin concentrations (5 microM), (ii) a "digitonin-sensitive" cytoplasmic protein pool, which required higher concentrations of digitonin for release (10 microM) and included TyrOHase and PMTase, and (iii) the chromaffin granule, which was insensitive to digitonin. Analysis of the rates of release of all of these proteins revealed that the rate of TyrOHase and PMTase release was slower at 10 microM than at 40 microM digitonin, while the rates of release of the other proteins were similar at both concentrations and varied in proportion to their respective sizes. Treatment with cytoskeletal disrupting agents had no effect on TyrOHase or PMTase efflux. These data suggest that TyrOHase and PMTase are in a detergent-labile association in the cell. This is consistent with the concept that TyrOHase and PMTase may be localized on the surface of the chromaffin granule.
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PMID:Restricted diffusion of tyrosine hydroxylase and phenylethanolamine N-methyltransferase from digitonin-permeabilized adrenal chromaffin cells. 287 56

We report here the isolation of a cDNA clone containing the full coding region of bovine phenylethanolamine N-methyltransferase (PNMTase, EC 2.1.1.28, S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase). The complete nucleotide sequence of the cDNA has been determined, and the amino acid sequence of PNMTase deduced. Cultured cells transfected with an expression vector containing this cDNA produced high levels of PNMTase enzymatic activity. Antibodies specific for tyrosine hydroxylase [EC 1.14.16.2, tyrosine 3-monooxygenase; L-tyrosine, tetrahydrobiopterine: oxygen oxidoreductase (3-hydroxylating)], the first enzyme in the catecholamine pathway, possess a striking affinity for the PNMTase protein synthesized in vitro. Comparison of the deduced amino acid sequence of bovine PNMTase to rat tyrosine hydroxylase reveals that PNMTase shares significant homology with tyrosine hydroxylase and supports previous protein and immunological data suggesting that the catecholamine biosynthetic enzymes are structurally related.
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PMID:Complete nucleotide and deduced amino acid sequence of bovine phenylethanolamine N-methyltransferase: partial amino acid homology with rat tyrosine hydroxylase. 287 53

Rat brain and adrenal gland were analyzed by hybridization histochemistry using an RNA probe complementary to mRNA for tyrosine 3-hydroxylase (TyrOHase; tyrosine 3-monooxygenase, EC 1.14.16.2), by immunohistochemistry using TyrOHase antiserum, and by retrograde tracing using the fluorescent compound Fast blue. Cell bodies in the ventral mesencephalon contained mRNA for TyrOHase, and these cells were also TyrOHase immunoreactive. After injection of Fast blue into the striatum, such double-labeled cells in addition contained the retrograde tracer, showing that these cells send axonal projections to the injection site. These results show that hybridization histochemistry can be used to identify transmitter-specific neuron populations and that their projections can be established.
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PMID:Tyrosine 3-hydroxylase in rat brain and adrenal medulla: hybridization histochemistry and immunohistochemistry combined with retrograde tracing. 287 60

Tyrosine hydroxylase [TyrOHase, tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (2-hydroxylating), EC 1.14.16.2] is the rate-limiting enzyme in the synthetic pathway of catecholamines and is expressed by neurons containing dopamine, norepinephrine, and epinephrine. TyrOHase is present in high concentrations in the caudate nucleus and putamen, where nearly all of it is contained in axons of the dopaminergic mesostriatal pathways. We have employed three different polyclonal antibodies directed against TyrOHase, one tested here for specificity by two-dimensional gel electrophoresis, to reexamine the anatomic distribution of fibers expressing TyrOHase-like immunoreactivity in the striatum of mature human, monkey, and cat brains. The findings suggest that this distribution is distinctly inhomogeneous. The macroscopic compartments known as striosomes have low TyrOHase-like immunoreactivity relative to the surrounding extrastriosomal matrix. These observations add to evidence that dopaminergic modulation of neural processing in the mature striatum is organized in accordance with striosomal architecture and suggest that part of the mechanism for such differentiation may involve presynaptic differences in enzymatic regulation of dopamine content in and out of striosomes.
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PMID:Differences in tyrosine hydroxylase-like immunoreactivity characterize the mesostriatal innervation of striosomes and extrastriosomal matrix at maturity. 287 89

A rat tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] cDNA probe was used for in situ hybridization studies on histological sections through the locus coeruleus, substantia nigra, and the ventral tegmental area of the rat brain. Experimental conditions were established that yielded no background and no signal when pBR322 was used as a control probe. Using the tyrosine hydroxylase probe, we ascertained the specificity of the labeling over catecholaminergic cells by denervation experiments and comparison of the hybridization pattern with that of immunoreactivity. The use of 35S-labeled probe enabled the hybridization signal to be resolved at the cellular level. A single injection of reserpine into the rat led to an increase of the intensity of the autoradiographic signal over the locus coeruleus area, confirming an RNA gel blot analysis. The potential of in situ hybridization to analyze patterns of modulation of gene activity as a result of nervous activity is discussed.
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PMID:Modulation of tyrosine hydroxylase gene expression in the central nervous system visualized by in situ hybridization. 288 13

We have found that the 14-3-3 protein, an acidic neuronal protein, is substantially identical to the 'activator' protein [(1981) J. Biol. Chem. 256, 5404-5409] that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+, calmodulin dependent protein kinase II. This finding is based on the remarkable similarity of both these proteins in physicochemical, biochemical and immunochemical properties, as well as on detection for the 14-3-3 protein of an activator activity towards tryptophan 5-monooxygenase. The result suggests that the 14-3-3 protein plays a role in the regulation of serotonin and noradrenaline biosynthesis in brain.
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PMID:Brain 14-3-3 protein is an activator protein that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+,calmodulin-dependent protein kinase II. 288 29


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