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)

Changes in the high-threshold calcium current (Ica) induced by intracellular administration of L-tyrosine and L-phenylalanine have been studied on internally perfused PC 12 pheochromocytoma cells using whole-cell voltage-clamp technique. L-tyrosine (20 microM/l) not only prevented a decay of Ica occurring during intracellular perfusion but induced also its transient recovery. In contrast, L-phenylalanine (20 microM/l) accelerated a decline of Ica. Replacement of ATP in the perfusing solution by an equivalent amount of ADP (2 mmol/l) did not alter the effect of amino acids. alpha-methyl-D, L-tyrosine (a specific blocker of tyrosine hydroxylase) caused the effect similar to that of L-tyrosine.
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PMID:[Effect of intracellular administration of L-tyrosine and L-phenylalanine on voltage dependent calcium current in PC 12 pheochromocytoma cells]. 167 91

Involvement of Ca2+/calmodulin-dependent protein kinase II (Ca2+/CaM-kinase II) on the phosphorylation of tyrosine hydroxylase (TH, EC.1.14.16.2) in rat pheochromocytoma, PC12h cells was examined using KN-62, 1-[N,O-Bis(5-isoquinolinsulfonyl)-N-methyl-L-tyrosyl]-4-phenylpipe razine, a selective inhibitor of Ca2+/CaM-kinase II. Both the enhanced phosphorylation of TH and the activated L-3,4-dihydroxyphenylalanine (DOPA) formation in the high K+ depolarization were inhibited by 10 microM KN-62. After incubation of PC12h cells with 10 microM KN-62 for 1 hr, the activation of TH with 3 min incubation of 56 mM K+ was reduced to the basal activity. However, KN-62 did not directly affect the activity of purified rat TH at pH 6.0 or 7.0. These results indicate that Ca2+/CaM-kinase II phosphorylates and activates TH of PC12h cells in the high K+ depolarization.
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PMID:A selective Ca2+/calmodulin-dependent protein kinase II inhibitor, KN-62, inhibits the enhanced phosphorylation and the activation of tyrosine hydroxylase by 56 mM K+ in rat pheochromocytoma PC12h cells. 167 65

We examined whether drugs that block calcium, prostaglandins, free radicals, and endorphin release could modify cerebral blood flow or nerve tissue pathology following a focal cerebrovascular lesion. Cats were randomly divided into six groups and were subjected to standard middle cerebral artery occlusion (MCAO) performed using a transorbital approach. One hour after MCAO, cats received the following compounds intravenously: (i) saline (CS), 1.5 mL/kg or polyethylene glycol, 300 micrograms (CP); (ii) naloxone (NX), 2 mg/kg; (iii) nimodipine (NM), 1 microgram.kg-1.min-1 x 60 min; (iv) dimethyl sulfoxide (DS), 0.9 g/kg in a 40% solution; (v) prostacyclin (PGI2), 200 ng.kg-1.min-1 for 60 min; or (vi) DS-PGI2 combined. At 1-h intervals, local CBF was recorded from the cortical tissue proximal and distal to the MCAO site using the hydrogen clearance method. Five hours after MCAO, cortical tissue was removed for catecholamine histofluorescence or perfused for tyrosine hydroxylase immunoreactive axon examination. Treatment with NX, NM, CP, or CS had no effect on either CBF or cortical tissue neurotransmitter morphology. PGI2 showed a transiently modest but significant increase of CBF, while DS provided moderate protection of catecholaminergic fibers and increased CBF by 27% after MCAO. The combination of DS-PGI2 resulted in significant cytoprotection of cortical catecholaminergic fibers and generated a sustained CBF increase of 68% of control values. These findings suggest that combining DS with PGI2 can yield a synergic effect with respect to cortical neurotransmitter and CBF protection after MCAO.
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PMID:Synergic activity of combined prostacyclin: dimethyl sulfoxide in experimental brain ischemia. 167 27

We have investigated the ability of exogenous gangliosides to modulate nerve growth factor (NGF) signal transduction in PC12 cells. The effects of exogenous ganglioside GM1 on multiple protein kinase activities were assayed by analyzing site-specific serine phosphorylation of tyrosine hydroxylase (TyrOHase) by two-dimensional phosphopeptide mapping. In the presence of NGF, exogenous GM1 (1-10 microM) increased 32P incorporation into TyrOHase phosphopeptide T2, a Ca2+/calmodulin-dependent protein kinase substrate whose phosphorylation is not normally affected by NGF treatment. In the absence of NGF, GM1 treatment had no significant effects on TyrOHase phosphorylation. The removal of extracellular Ca2+ or blockade of dihydropyridine-sensitive Ca2+ channels prevented the GM1-induced increases in 32P incorporation into phosphopeptide T2. Exogenous GM1 also potentiated K+ depolarization-induced increases in the phosphorylation of TryOHase. These results suggest that the stimulatory effects of exogenous GM1 ganglioside on NGF actions may be due to its ability to potentiate a Ca(2+)-dependent signaling pathway.
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PMID:Stimulation of a Ca(2+)-dependent protein kinase by GM1 ganglioside in nerve growth factor-treated PC12 cells. 167 13

We studied the effect of brain natriuretic peptide (BNP) on the accumulation of cyclic GMP and the phosphorylation and activity of tyrosine hydroxylase, compared with that of atrial natriuretic peptide (ANP), in cultured bovine adrenal medullary cells. 1. BNP as well as ANP increased cellular cyclic GMP accumulation in a concentration-dependent manner (10-1000 nmol/l). BNP (1 mumol/l) and ANP (1 mumol/l) produced a 60-fold and 30-fold increase in cyclic GMP accumulation, respectively. 2. The stimulatory effects of BNP and ANP on cyclic GMP accumulation were observed even when Ca2+ or Na+ was removed from the incubation medium. 3. 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, inhibited the stimulatory effect of BNP on cyclic GMP accumulation in a concentration-dependent manner (1-100 nmol/l). Furthermore, the BNP-induced accumulation of cyclic GMP was attenuated by forskolin (1 mumol/l), an activator of adenylate cyclase. 4. BNP (1 mumol/l) and ANP (1 mumol/l) caused a significant increase in phosphorylation and activity of tyrosine hydroxylase in the cells. 5. In digitonin-permeabilized cells, cyclic GMP (1-100 mumol/l) activated tyrosine hydroxylase in the presence of ATP and Mg2+. These results suggest that BNP stimulates the accumulation of cyclic GMP in a manner similar to that of ANP. The increased accumulation of cyclic GMP by these peptides may be negatively modulated by protein kinase C and cyclic AMP and may cause the phosphorylation and activation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.
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PMID:Stimulatory effects of brain natriuretic peptide on cyclic GMP accumulation and tyrosine hydroxylase activity in cultured bovine adrenal medullary cells. 167 41

Previous studies have shown that insulin-like growth factor-I (IGF-I) enhances secretagogue-stimulated Ca2+ uptake and catecholamine release in bovine chromaffin cells. This report describes the effect of IGF-I on the activity of tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2), the major regulatory enzyme in the pathway of catecholamine biosynthesis. Tyrosine hydroxylase activity was assayed by measuring 3,4-dihydroxyphenylalanine (Dopa) accumulation in the presence of brocresine, an inhibitor of Dopa decarboxylase. Chromaffin cells cultured in serum-free medium produced approximately 40% less Dopa when stimulated by 55 mM K+ than did cells that had been cultured in the presence of serum. Incubation of cells for 3 days in serum-free medium containing 10 nM IGF-I restored high K(+)-stimulated Dopa accumulation to a level comparable to that seen in cells cultured continuously in serum-containing medium. In eight experiments, IGF-I increased high K(+)-stimulated Dopa accumulation (expressed as picomoles per minute per milligram of protein) by 96 +/- 13%. IGF-I increased the protein content of chromaffin cells by approximately 30%; consequently, its effect on tyrosine hydroxylase activity was even greater when Dopa synthesis was expressed as picomoles per minute per 10(7) cells. IGF-I also enhanced the rate of Dopa accumulation in cells stimulated by dimethylphenylpiperazinium, 8-bromo-cyclic AMP, phorbol 12,13-dibutyrate, or Ba2+. The effect of IGF-I on high K(+)-stimulated tyrosine hydroxylase activity was measurable when enzyme activity was assayed in vitro, suggesting that this effect was due to a stable modification of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factor-I enhances tyrosine hydroxylase activation in bovine chromaffin cells. 168 Jan 64

Immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the rat forebrain were analyzed quantitatively to confirm our previous results that the activities of central catecholamine-synthesizing enzymes are regulated by a calcium-calmodulin-dependent system. The adjacent slices of adult rat brain were stained immunohistochemically for tyrosine hydroxylase and for calmodulin, and the distributions and amounts of these proteins were measured by a fluorescence microphotometry system that was developed in our laboratory. Immunohistochemical fluorescence intensity was measured stepwise at 40 microns intervals through a 6 microns phi (on the slice) pin hole. Each stained brain slice was divided into approximately 100,000 areas, and measured for fluorescence intensity and displayed two- and three-dimensionally. Immunoreactive staining of tyrosine hydroxylase and calmodulin was observed in almost all areas of the brain, but its intensity varied. The relatively high levels of calmodulin could be observed in brain regions with high levels of tyrosine hydroxylase distribution, though high levels of tyrosine hydroxylase could not always be observed in brain regions where high levels of calmodulin were distributed. In the present study, high levels of tyrosine hydroxylase and calmodulin were distributed in the nucleus accumbens septi and the lateral part of the neostriatum regions in which the amount of dopamine was increased by the intraventricular administration of calcium. These findings suggest that the synthesis of central catecholamines is regulated by a calcium-calmodulin-dependent system.
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PMID:Multiple analysis of tyrosine hydroxylase and calmodulin distributions in the forebrain of the rat using a microphotometry system. 168 18

The effects of GABA and GABA agonists on calcium and depolarization-dependent stimulation of tyrosine hydroxylase activity in striatal slices were studied. gamma-Aminobutyric acid and (-)baclofen inhibited, while muscimol and (+)baclofen did not affect, the stimulation of tyrosine hydroxylase. The inhibitory effect of GABA and (-)baclofen was blocked by the GABAB antagonist, phaclofen but not by the GABAA antagonist, picrotoxin. The data suggest that the activity of tyrosine hydroxylase on dopaminergic nigrostriatal terminals may be modulated by GABA via GABAB receptors.
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PMID:Gamma-aminobutyric acid (GABAB) receptor-mediated inhibition of tyrosine hydroxylase activity in the striatum of rat. 168 45

This article focuses on the role of protein phosphorylation, especially that mediated by protein kinase C (PKC), in neurotransmitter release. In the first part of the article, the evidence linking PKC activation to neurotransmitter release is evaluated. Neurotransmitter release can be elicited in at least two manners that may involve distinct mechanisms: Evoked release is stimulated by calcium influx following chemical or electrical depolarization, whereas enhanced release is stimulated by direct application of phorbol ester or fatty acid activators of PKC. A markedly distinct sensitivity of the two pathways to PKC inhibitors or to PKC downregulation suggests that only enhanced release is directly PKC-mediated. In the second part of the article, a framework is provided for understanding the complex and apparently contrasting effects of PKC inhibitors. A model is proposed whereby the site of interaction of a PKC inhibitor with the enzyme dictates the apparent potency of the inhibitor, since the multiple activators also interact with these distinct sites on the enzyme. Appropriate PKC inhibitors can now be selected on the basis of both the PKC activator used and the site of inhibitor interaction with PKC. In the third part of the article, the known nerve terminal substrates of PKC are examined. Only four have been identified, tyrosine hydroxylase, MARCKS, B-50, and dephosphin, and the latter two may be associated with neurotransmitter release. Phosphorylation of the first three of these proteins by PKC accompanies release. B-50 may be associated with evoked release since antibodies delivered into permeabilized synaptosomes block evoked, but not enhanced release. Dephosphin and its PKC phosphorylation may also be associated with evoked release, but in a unique manner. Dephosphin is a phosphoprotein concentrated in nerve terminals, which, upon stimulation of release, is rapidly dephosphorylated by a calcium-stimulated phosphatase (possibly calcineurin [CN]). Upon termination of the rise in intracellular calcium, dephosphin is phosphorylated by PKC. A priming model of neurotransmitter release is proposed where PKC-mediated phosphorylation of such a protein is an obligatory step that primes the release apparatus, in preparation for a calcium influx signal. Protein dephosphorylation may therefore be as important as protein phosphorylation in neurotransmitter release.
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PMID:The role of protein kinase C and its neuronal substrates dephosphin, B-50, and MARCKS in neurotransmitter release. 168 57

A method for demineralization of bone, preserving the antigenicity of neuroactive peptides, was developed. In all parts of rat long bones, nerves immunoreactive to substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were detected after immunohistochemical staining. The majority of nerves were vascular, although several non-vascular endings were observed at the growth plate and amidst marrow cells. An abundance of nerves were demonstrated near the epiphyseal plate and in the periosteum, regions of high osteogenic activity. The occurrence of different nerve types was analyzed at different stages of heterotopic osteogenesis, induced by allogeneic bone matrix. Nerve fibres immunoreactive to SP, CGRP, NPY and TH occurred amidst differentiating chondroblastic cells in the second week. They gradually increased in number during the ensuing eight weeks. In an in vitro study of osteoblastic cells (UMR 106-01, ROS 17/2.8, Saos-2, MC3T3-E1) receptors to CGRP, VIP, noradrenaline (NA) and NPY were demonstrated as assessed by analysis of cyclic AMP formation. In UMR cells, NPY inhibited the effects of NA and parathyroid hormone (PTH), which is the first demonstration of a receptor interaction between a local neuropeptide and a systemic calcium regulating hormone. The combined findings indicate a neuroendocrine influence on bone physiology.
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PMID:Neuroendocrine peptides in bone. 172 76


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