Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Clonazepam at two doses of 1 mg/kg i.p. significantly decreased 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents in the rat caudatus and cortex but not so in the olfactory tubercle, septum and hypothalamus. The drug decreased dopamine (DA) turnover rate in the caudatus, but did not inhibit tyrosine hydroxylase activity. The drug significantly enhanced stereotyped behavior induced by apomorphine and d-methamphetamine. Clonazepam enhanced apomorphine-induced decrease in striatal HVA, and cortical DOPAC and HVA contents, and d-methamphetamine-induced decrease in cortical DOPAC content. Reserpine pretreatment did not affect apomorphine-induced stereotypy and its enhancement with clonazepam. The drug did not activate adenylate cyclase nor DA-sensitive adenylate cyclase in the striatal homogenates and did not change cyclic AMP content in the caudatus. The drug inhibited phosphodiesterase activity in caudate and cortical homogenates but not in vivo. Clonazepam did not alter ChAc and AChE activities in the caudatus, 6 other cerebral regions and the spinal area. Clonazepam also decreased NE turnover in the caudatus and 5-HIAA contents in the brainstem area. These neurochemical and behavioral effects of clonazepam indicate probable postjunctional DA stimulation in the striatum and cortex of the type not linked with adenylate cyclase and phosphodiesterase but probably due to activation of inhibitory gamma-amino butyric acid (GABA) neurons on the strio-nigral pathway.
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PMID:[Influence of clonazepam, an anticonvulsant benzodiazepine drug, on the rat brain monoamine containing neurons especially on dopaminergic neurons (author's transl)]. 20 28

Low doses of d-amphetamine (d-AMP) produced a 50% or greater decrease in the firing rates of both dopamine (DA) neurons (substantia nigra zone compacta) and norepinephrine (NE) neurons (locus coeruleus). However, pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT) blocked the d-AMP-induced reduction in DA neuron firing rate, but had no effect on the d-AMP-induced reduction in NE cell firing rate. Similarly, alpha-MT administered subsequent to d-AMP readily reversed the d-AMP-induced decrease in the firing rates of DA cells, but caused no significant reversal in NE cell firing rates. These electrophysiological findings, in conjunction with biochemical and behavioral data, support the hypothesis that there is a difference in the DA and NE neurotransmitter storage mechanism. In the DA neuron, there appears to be a slow transfer between stored and readily-releasable (newly synthesized) amine pools so that, following synthesis inhibition, there is little DA available for release. However, in the NE neuron, there is a more rapid mobilization of stored amine to readily releasable sites, such that d-AMP continues to cause the release of NE even though synthesis of transmitter is blocked.
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PMID:Differences in norepinephrine and dopamine neurotransmitter storage systems. 22 44

Membrane-permeable derivatives of cyclic AMP (cAMP) produced concentration-dependent increases in activity of tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2) in membrane-limited nerve endings (synaptosomes) prepared from three regions of rat brain. Increased hydroxylation occurred even after preincubation and removal of dibutyryl cyclic AMP. In all brain regions, the hydroxylation of phenylalanine and tyrosine was increased, but dibutyryl cAMP had little effect on activity of tryptophan hydroxylase, no effect on aromatic amino-acid decarboxylase, on uptake of tyrosine or phenylalanine, uptake or efflux of dopamine, or distribution of hydroxylase between cytoplasmic and particulate components of the synaptosomes. Dibutyryl cAMP decreased inhibition of catecholamine synthesis in synaptosomes by dopamine and apomorphine. In a soluble preparation of striatal tyrosine hydroxylase, activity was increased by addition of lower concentrations of cAMP or dibutyryl cAMP than with unbroken nerve endings, when subsaturating concentrations of tyrosine and cofactor were employed, while butyrate, chloride, 5'-AMP, ADP, ATP, and cyclic GMP had no activating effect. Increased activity of soluble tyrosine hydroxylase was reflected in increased affinity (Km) for substrate and cofactor and decreased affinity (Ki) for inhibitory end-product (dopamine), suggesting a change in the physical-chemical state of the enzyme or an activator molecule. Cyclic AMP may activate tyrosine hydroxylase during periods of increased neuronal activity.
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PMID:Activation by cyclic 3':5'-adenosine monophosphate of tyrosine hydroxylase in the rat brain. 23 58

Sympathetic ganglia from 13- to 15-day-old embryonic chicks were cultured for up to 2 days in Leighton tubes. The influence of hydrocortisone and ACTH added to the culture medium on the enzymes monoamine oxidase (MAO) and tyrosine hydroxylase was studied. Hydrocortisone (5 times 10(-5)M) had no effect on tyrosine hydroxylase but increased MAO activity by up to 46 percent over control values under conditions of low or zero nerve growth factor (NGF) concentration. ACTH also increased ganglionic MAO activity, the effect again depending on NGF concentration. This time the maximal response (an increase of 50 percent over controls) was seen at high NGF concentrations. This response was similar to the effect of 1 mM dibutyryl cyclic AMP, and was blocked by 1 times 10-5 M propranolol and 10 muM prostaglandin E(1). ACTH only slightly increased tyrosine hydroxylase activity and this effect was due to a small (18 percent) increase in sympathetic neurone number. Guanosine 5-diphosphate (0.5 mM) was found to increase tyrosine hydroxylase activity by 57 percent and this effect was blocked by the presence of ACTH.
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PMID:The effect of hydrocortisone and adrenocorticotrophic hormone on monoamine oxidase and tyrosine hydroxylase in explant cultures of embryonic chick sympathetic ganglia. 23 5

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

alpha-MSH was found to decrease the recently characterized dopachrome tautomerase activity in cultures of B16/F10 mouse melanoma cells. Other stimulating agents of melanogenesis, like dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, theophylline, retinol, and retinoic acid, caused the same effect. The grade of inhibition depended on the nature of the agent and the time of exposure. In all cases, both melanin production and tyrosinase activity were activated by these treatments, although the grade of tyrosine hydroxylase and dopa oxidase stimulation was different. Moreover, no correlation among the intensities of dopachrome tautomerase inhibition and tyrosinase activation by the tested agents could be obtained. The significance of these results in the regulation of mammalian melanogenesis is discussed.
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PMID:Alpha-MSH and other melanogenic activators mediate opposite effects on tyrosinase and dopachrome tautomerase in B16/F10 mouse melanoma cells. 132 99

Tryptic digestion of tyrosine hydroxylase (TH) isolated from rat adrenal glands labeled with 32Pi produced five phosphopeptides. Based on the correspondence of these phosphopeptides with those identified in TH from rat pheochromocytoma cells, four phosphorylation sites (Ser8, Ser19, Ser31, and Ser40) were inferred. Field stimulation of the splanchnic nerves at either 1 or 10 Hz (300 pulses) increased 32P incorporation into TH. At 10 Hz, the phosphorylation of Ser19 and Ser40 was increased, whereas at 1 Hz, Ser19, Ser31, and Ser40 phosphorylation was increased. Stimulation at either 1 or 10 Hz also increased the catalytic activity of TH, as measured in vitro (pH 7.2) at either 30 or 300 microM tetrahydrobiopterin. Nicotine (3 microM, 3 min) increased Ser19 phosphorylation, vasoactive intestinal polypeptide (10 microM, 3 min) increased Ser40 phosphorylation, and muscarine (100 microM, 3 min) increased TH phosphorylation primarily at Ser19 and Ser31. Vasoactive intestinal polypeptide, but not nicotine or muscarine, mimicked the effects of field stimulation on TH activity. Thus, the regulation of rat adrenal medullary TH phosphorylation by nerve impulses is mediated by multiple first and second messenger systems, as previously shown for catecholamine secretion. However, different sets of second messengers are involved in the two processes. The action of vasoactive intestinal polypeptide as a secretagogue involves the mobilization of intracellular calcium, whereas its effects on TH phosphorylation are mediated by cyclic AMP. This latter effect of vasoactive intestinal polypeptide and the consequent increase in Ser40 phosphorylation appear to be responsible for the rapid activation of TH by splanchnic nerve stimulation.
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PMID:Activation and multiple-site phosphorylation of tyrosine hydroxylase in perfused rat adrenal glands. 134 70

Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels of protein kinase activity. Other treatments known to either increase (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also found to increase or decrease, respectively, levels of cAMP-dependent protein kinase activity in this brain region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxylase in the rat locus coeruleus: effects of chronic stress and drug treatments. 134 39

The mouse tyrosine hydroxylase (TH) gene was isolated from a genomic library by cross-hybridization with human TH cDNA probe. Nucleotide sequence analysis of two overlapping genomic clones showed that this gene is split into 13 exons distributed about 7.5 kb in length. The transcription initiation site was determined by primer extension analysis with mouse adrenal gland poly(A)+RNA. The structure of the mouse TH gene was similar to that of the human TH gene, but it contained neither the alternative splice donor site around the 3'-end of the first exon nor an independent exon corresponding to the second exon of the human TH gene. There were the canonical TATA and GC boxes, cyclic AMP responsive element (CRE), and AP1 binding site in the 5'-flanking region of the mouse TH gene.
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PMID:Structure of the mouse tyrosine hydroxylase gene. 134 48

Investigation of neuroendocrine genes has revealed that transcription is regulated via multiple DNA binding sites, including the cyclic AMP response element (CRE). We show here that for the neuronal and chromaffin-specific gene tyrosine hydroxylase (TH), a 70-bp region (-229 to -160) lacking the CRE is sufficient, in either orientation, to confer levels of chloramphenicol acetyltransferase reporter expression equivalent to or greater than that conferred by 4.8 kb of the rat TH enhancer/promoter region. The 70-bp region contains potential binding sites for AP2, AP1, E2A/MyoD, and POU transcription factors, and functions when linked to the TH promoter, but not when joined to a heterologous RSV promoter. This demonstrates that promoter as well as enhancer elements are important for TH expression. In gel-shift assays, the 70-bp fragment forms a cell type-specific complex with nuclear extracts from TH-expressing cells. which is effectively competed by an oligonucleotide containing AP2, AP1, and E2A/MyoD (E box) sites, but not by one containing the POU site. These data suggest that the AP2, AP1, and/or E box sites may be involved in forming the cell-specific complex. Although it lacks an authentic CRE, the 70-bp region also mediated a twofold transcriptional response to forskolin, equivalent to that found with the endogenous gene. A different region (-60 to -29) bearing a consensus CRE mediated a sixfold increase in transcription in response to forskolin, but only minimally activated basal transcription from the TH promoter in the absence of forskolin.
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PMID:Sequences that direct rat tyrosine hydroxylase gene expression. 134 42


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