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)

In an attempt to determine if alterations in intraneuronal Ca2+ may regulate tyrosine hydroxylase activity, brain slices were subjected to experimental manipulations known to increase the intraneuronal concentration of free Ca2+ ions. Incubation of either striatal or olfactory tubercle slices in a Na+-free medium for 15 min at 37 degrees resulted in a marked increase in the activity of tyrosine hydroxylase present in the 20,000 g supernatant fraction of homogenates prepared from the slices. Tyrosine hydroxylase isolated from slices previously incubated in a Na+-free, choline-enriched medium or in a Na+-free, sucrose-enriched medium exhibited maximal activities when assayed at pH 6.0 and 7.0, respectively. However, the percentage stimulation of enzyme activity induced by incubation of the slices in a Na+-free medium was maximal when the enzyme assays were performed at pH 7.0. The observed increase in enzyme activity seems to be mediated by a decrease in the apparent Km of the enzyme for pteridine cofactor, regardless of whether the kinetic enzyme analyses were conducted at pH 6.0 or 7.0, and by an increase in the Ki of the enzyme for end-product inhibitor dopamine. The apparent kinetic changes in the enzyme do not seem to result from alterations in the endogenous dopamine content of the slices, and they are independent of any increase in dopamine release that might have occurred as a response to the augmented intraneuronal Ca2+ concentration. Furthermore, the activation of tyrosine hydroxylase produced by incubating slices in a Na+-free medium is observed even in slices depleted of dopamine by pretreatment of rats with reserpine 90 min before preparation of brain slices. The activation of tyrosine hydroxylase observed under these experimental conditions does not seem to be mediated by cAMP or by a cAMP-dependent phosphorylation process. It is suggested that the changes in tyrosine hydroxylase reported are mediated primarily by a rise in the free Ca2+ concentration within the nerve tissue. These observations are consistent with the hypothesis that the kinetic activation of tyrosine hydroxylase produced after depolarization of central dopaminergic neurons may occur through a Ca2+-dependent even other than transmitter release.
 ...
PMID:Tyrosine hydroxylase regulation: apparent kinetic alterations following incubation of brain slices in a sodium-free medium. 610 91

The kinetic properties of soluble tyrosine hydroxylase from rat striatum and the activation of the enzyme by the polyanion heparin were assessed as a function of the monovalent cations K+, Na+, tetramethylammonium (TMA+), and Tris. Substitution of K+ or Na+ for TMA+ or Tris can alter the kinetic properties of tyrosine hydroxylase in the absence of heparin the nature of the interaction of the enzyme with heparin and also the kinetic properties of the heparin-activated enzyme. The data suggest that monovalent cations can support unique conformational states of the enzyme.
 ...
PMID:Monovalent cations and striatal tyrosine hydroxylase. 611 90

The carboxylic ionophore monensin inhibits the activity of tyrosine 3-monooxygenase and decreases the rate of catecholamine synthesis in pheochromocytoma cells incubated in vitro. The ionophore inhibits dopa production in intact pheochromocytoma cells, but does not itself inhibit tyrosine 3-monooxygenase and does not produce a stable inactivation of the enzyme as assayed in cell-free extracts of the cells. The inhibition of dopa production by monensin is dependent upon extracellular Na+, but does not require extracellular Ca++. This effect of monensin is more pronounced in the presence of pargyline. In the absence of pargyline, monensin also depletes the cells of norepinephrine and increases the accumulation of the deaminated norepinephrine metabolite, dihydroxyphenylglycol. Finally, monensin increases the release of catecholamines from isolated chromaffin granules. These results are consistent with the hypothesis that monensin causes the release of norepinephrine from chromaffin granules into the cytoplasm of pheochromocytoma cells and that the increase in cytoplasmic norepinephrine inhibits tyrosine 3-monooxygenase activity.
 ...
PMID:Monensin inhibits catecholamine synthesis in pheochromocytoma cells. 612 83

Suspension cultures of purified bovine adrenal chromaffin cells incorporated 32P from exogenous 32Pi into a protein of approximately M4 = 60,000 (isolated by discontinuous, sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis). Phosphorylated tyrosine hydroxylase, purified from chromaffin cell supernatants by immunoprecipitation, co-migrated with the Mr = 60,000 band. Tryptic fragments prepared fom either the Mr congruent to 60,000 band or the immunoprecipitated tyrosine hydroxylase band were analyzed after separation with two-dimensional electrophoresis/chromatography. Two distinct 32P-peptides were present in either sample. After a 2-3-min lag period. 32P incorporation into both peptides was relatively linear with time for at least 20 min. In the presence of calcium, exogenous acetylcholine (100 microM) increased 32P incorporation into both of the 32P-labeled tryptic peptides whereas 8-bromo-cAMP (1 mM) increased 32P incorporation into only one of the two. Ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and MnCl2 inhibited the acetylcholine-induced phosphorylation of both tryptic peptides. Thus, tyrosine hydroxylase is phosphorylated in situ at more than one site, and the phosphorylation of these sites is affected differently by acetylcholine and 8-bromo-cAMP. The data imply that kinase activity other than (or in addition to) cAMP-dependent protein kinase activity attends tyrosine hydroxylase in the intact chromaffin cells and that multiple kinase activities may be involved in the short term regulation of catecholamine biosynthesis by afferent activity.
 ...
PMID:Multiple site phosphorylation of tyrosine hydroxylase. Differential regulation in situ by a 8-bromo-cAMP and acetylcholine. 612 38

Membranes of the secretory vesicles from bovine adrenal medulla were investigated for the presence of the endogenous protein phosphorylation activity. Seven phosphoprotein bands in the molecular weight range of 250,000 to 30,000 were observed by means of the sodium dodecyl sulphate electrophoresis and autoradiography. On the basis of the criteria of molecular weight, selective stimulation of the phosphorylation by cyclic AMP (as compared with cyclic GMP) and immunoprecipitation by specific antibodies, band 5 (molecular weight 60,300) was found to represent the phosphorylated form of the secretory vesicle-bound tyrosine hydroxylase. The electrophoretic mobility, the stimulatory and inhibitory effects of cyclic AMP in presence of Mg2+ and Zn,2+ respectively, and immunoreactivity toward antibodies showed band 6 to contain two forms of the regulatory subunits of the type II cyclic AMP-dependent protein kinase, distinguishable by their molecular weights (56,000 and 52,000, respectively). Phosphorylation of band 7 (molecular weight 29,800) was stimulated about 2 to 3 times by Ca2+ and calmodulin in the concentration range of both agents believed to occur in the secretory tissues under physiological conditions.
 ...
PMID:3',5'-cyclic adenosine monophosphate- and Ca2+-calmodulin-dependent endogenous protein phosphorylation activity in membranes of the bovine chromaffin secretory vesicles: identification of two phosphorylated components as tyrosine hydroxylase and protein kinase regulatory subunit type II. 613 Nov 3

A rapid and simple simultaneous micropurification procedure of tyrosine hydroxylase (TH) and dihydropteridine reductase (DPR) was developed from soluble supernatants of 1 to 2 g of rat adrenal gland or caudate nucleus. All purification procedures for the two enzymes were complete within 3 days. The recovery of TH and DPR was reproducible and approximately 20 and 40%, respectively. Purification procedure for TH involved chromatographies with DEAE-Sephacel, Bio-Gel A-1.5 m, and heparin-Sepharose. As judged by gel filtration and sodium dodecyl sulfate-gel electrophoresis, the enzyme purified from each tissue appeared to be homogeneous and was composed of an identical subunit, each possessing a Mr of 60,000. With DEAE-Sephacel column chromatography, TH was separated completely from DPR. DPR was purified by subsequent chromatographies with Sephadex G-50 and blue Sepharose to a purity of 50%. DPR in adrenals and brain was found to be a NADH-dependent type. This micropurification procedure is applicable to assessing the molecular properties of TH modified physiologically or pharmacologically in vivo, and to getting a small amount of the pure enzyme as antigen for producing its antibody.
 ...
PMID:Simultaneous simple purification of tyrosine hydroxylase and dihydropteridine reductase. 613 72

Catecholamine levels and activity of catecholamine-forming enzymes have been quantitated in adrenal glands of Dahl sodium-resistant (R) and sodium-sensitive (S), genetically hypertensive rats maintained on low- or high-salt diets. A high-salt diet results in markedly different changes in the catecholamine metabolism in R and S rats. In R rats, a high-salt diet reduces the activities of tyrosine 3-hydroxylase (TH;-5%) and dopamine beta-hydroxylase (DBH; -18%) as well as the levels of all catecholamines (dopamine -28%, norepinephrine -11%, and epinephrine -28%). In contrast, S rats fed a high-salt diet showed increased TH (+7%) and phenylethanolamine N-methyltransferase (+16%) activities as well as an increased content of adrenal norepinephrine (+13%) and epinephrine (+21%). These findings demonstrate a genetic difference in the effects of a high-salt diet on the synthesis of catecholamines in the adrenal gland of Dahl R and S rats. Hypertension only occurs in S rats on a high-salt diet, concomitant with large increases in the formation of adrenal catecholamines.
 ...
PMID:Increased adrenal catecholamines in salt-sensitive genetically hypertensive Dahl rats. 613 26

Regulation of the putative peptide neurohumour [Leu]enkephalin and the catecholaminergic enzymes tyrosine hydroxylase and phenylethanolamine-N-methyl-transferase was examined in the rat adrenal medulla in vivo and in vitro. Surgical denervation of the adrenal gland or pharmacologic blockade of synaptic transmission, treatments known to decrease catecholamine traits, increased [Leu]enkephalin content. Medullas explanted to culture exhibited a 50-fold rise in [Leu]enkephalin in 4 days, whereas tyrosine hydroxylase remained constant, and phenylethanolamine-N-methyltransferase decreased to a new baseline level. Veratridine-induced depolarization prevented the accumulation of [Leu]enkephalin, an effect that was blocked by tetrodotoxin, which antagonizes transmembrane Na+ influx. These studies suggest that enkephalinergic and catecholamine characters are differentially regulated by impulse activity and depolarization in the adrenal medulla.
 ...
PMID:Impulse activity differentially regulates [Leu]enkephalin and catecholamine characters in the adrenal medulla. 614 83

Triamterene, which is structurally similar to the natural cofactor of tyrosine hydroxylase, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, inhibited tyrosine hydroxylase in rat adrenal gland homogenates and was found to be a competitive inhibitor of the synthetic cofactor 6,7-dimethyl-5,6,7,8-tetrahydrobiopterin. When triamterene (30 mg/kg i.p.) was administered to rats, a significant decrease in the adrenal, whole brain and kidney enzyme activities was observed after 90 min; if the drug was given orally, the diuretic affected only adrenal tyrosine hydroxylase. In both cases the drug decreased potassium excretion to 1/5 of control values and increased the excretion of sodium. Catecholamine levels in atria, kidneys, adrenal glands and whole brain were not affected in acute experiments. Chronic treatment (triamterene 30 mg/kg p.o. twice daily during 4 days) inhibited tyrosine hydroxylase and decreased catecholamine levels in the kidneys. Low potassium excretion was observed throughout the 4 days of treatment. In these chronic experiments the inhibition of the adrenal enzyme seen in acute treatments was not observed. This recovery cannot be explained by an increase in the adrenal biopterin levels. It could be mediated by an induction of the adrenal tyrosine hydroxylase.
 ...
PMID:Effect of triamterene on tyrosine hydroxylase activity. 614 69

Tyrosine hydroxylase can be measured by release of tritiated water from labeled tyrosine, and the assay method has now been modified to allow recovery of 3H2O from the reaction mixture in a much more rapid and less tedious manner than previously possible. In the new method, the tyrosine hydroxylase reaction is stopped with sodium carbonate, pH 11.6. At this pH the tritium in 3H2O, but not other 3H species, is extracted into an organic scintillant containing 25% isoamyl alcohol, toluene, 2,5-diphenyloxazole, and p-bis-[2-(5-phenyloxazolyl)]benzene. The selective extraction occurs by means of exchange of tritium in 3H2O with the hydroxyl proton of isoamyl alcohol. It is the [3H]isoamyl alcohol that is then extracted into the scintillant and quantified by liquid scintillation spectrometry. Although the organic extraction method is somewhat less sensitive than the more frequently used ion-exchange method for isolating the 3H2O formed in the tyrosine hydroxylase reaction, it is much more rapid, as well as cost effective, since the enzyme reaction, extraction, and counting are carried out within the same vial.
 ...
PMID:A rapid and simplified assay method for tyrosine hydroxylase. 615 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>