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)

Monoaminergic synaptosomes have been isolated and purified from rat brain by immunomagnetophoresis. This novel technique uses magnetic beads to which Protein A is bound. Noradrenergic, dopaminergic, and serotonergic synaptosomes (previously cell-surface labelled with anti-dopamine-beta-hydroxylase, anti-tyrosine hydroxylase, and anti-tryptophan hydroxylase, respectively) may be isolated in a highly purified state. The synaptosomal subpopulations are recovered in a viable metabolic state and show glucose-stimulated respiration and Ca2(+)-dependent neurotransmitter release. A novel subtype of dopamine-beta-hydroxylase was found in dopaminergic terminals. No evidence for glutamate corelease from monoaminergic synaptosomes was obtained.
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PMID:Isolation of monoaminergic synaptosomes from rat brain by immunomagnetophoresis. 167 82

The mechanism of action of systemically administered (+/-)-MDMA (3,4-methylenedioxymethamphetamine) on spontaneously active neurons in the medial prefrontal cortex (mPFc) of chloral hydrate anesthetized rats was examined using standard single unit extracellular recording techniques. Intravenously administered MDMA dose-dependently decreased the firing rates of the majority of mPFc neurons in control rats. In contrast, in rats that were pretreated with p-chlorophenylalanine (PCPA), which depletes the brain serotonin (5-hydroxytryptamine, 5-HT) content by inhibiting tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of 5-HT, MDMA was largely ineffective in inhibiting the firing of mPFc cells. In PCPA-treated animals, the administration of 5-hydroxytryptophan (5-HTP), which presumably restored the brain 5-HT content, but not L-DOPA, reinstated MDMA's inhibitory action in PCPA-treated rats. In rats that were pretreated with alpha-methyl-p-tyrosine (AMPT), which depletes the brain dopamine (DA) content by inhibiting tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of DA, MDMA inhibited the firing of all of the mPFc cells. MDMA's effect on mPFc neurons was reversed by 5-HT receptor antagonists such as granisetron and metergoline. These results strongly suggest that MDMA exerts its action on mPFc cells indirectly by releasing endogenous 5-HT.
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PMID:The action of (+/-)-MDMA on medial prefrontal cortical neurons is mediated through the serotonergic system. 167 24

In situ hybridization (LARRSON and HOUGAARD 1990), using the APAAP complex, shows that many small and medium-sized neurons with signals of tryptophan hydroxylase mRNA are uniformly scattered throughout the rat's locus ceruleus, and that a few extrinsic neurons just ventro-medial to it also shows the hybridization signals. The specificity of this technique has been established by Northern blot hybridization. Synthesis of serotonin in intrinsic neurons is indicated not only by the results obtained from in situ hybridization, but also by the fact that, in distribution, masked serotonin cells, immunocytochemically revealed after pargyline and 5-hydroxytryptophan loading, correspond to the neurons showing mRNA hybridization signals. Identification of the same neurons in adjacent cryostat sections, immunostained alternately for serotonin or tyrosine hydroxylase after loading, provides evidence for the coexistence of serotonin and noradrenaline in a single neuron of this center. A few extrinsic, non-specific indoleamine cells located just ventro-medial to the center may be related to the lateralization of the raphe's neurons. The expression of tryptophan hydroxylase in CNS appears to be restricted to the specific regions such as the locus ceruleus and raphe's nuclei.
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PMID:An immunocytochemical study using the PAP method for tyrosine hydroxylase and serotonin in alternate sections, and in situ hybridization to detect tryptophan hydroxylase mRNA in the rat's locus ceruleus. 168 63

Levels of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (serotonin, 5-HT) and their metabolites, and the activities of tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH) and monoamine oxidase A and B (MAO-A and MAO-B) have been determined in the rat posterior thalamus after enucleation during postnatal development. DA and 5-HT turnover rate have been measured as 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) accumulation rates after central decarboxylase inhibition by 3-hydroxybenzylhydrazine (NSD-1015). The major changes were an increase in noradrenergic and serotoninergic metabolism in enucleated animals compared with control animals. A decrease of the MAO-A to MAO-B ratio during postnatal development was found.
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PMID:Effects of neonatal bilateral eye enucleation on postnatal development of the monoamines in posterior thalamus of the rat. 168 25

We have examined the expression of mRNAs encoding five major neurotransmitter-synthesizing enzymes in MAH cells, a clonal cell line derived by retroviral immortalization of a rat embryonic sympathoadrenal progenitor cell. These mRNAs include tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), tryptophan hydroxylase (TpH), and glutamic acid decarboxylases (GADs) 1 and 2. We find that MAH cells express high levels of TH mRNA and low levels of ChAT and TpH mRNAs. Neither GAD1 nor GAD2 mRNAs are detectable using an RNase protection assay with a detection limit of less than one transcript per cell. A similar pattern of mRNA expression is observed in postnatal superior cervical ganglia, adrenal medulla, and in PC12 cells. Transmitter synthesis and accumulation assays indicate that MAH cells can synthesize both catecholamines and acetylcholine. Thus the TH and ChAT mRNAs detected in these cells are likely to be translated into active enzyme. To corroborate these data obtained using MAH cells, we performed similar transmitter synthesis and accumulation assays on sympathoadrenal progenitors directly isolated from E14.5 fetal adrenal glands by fluorescence-activated cell sorting. These progenitor cells also synthesize and accumulate both catecholamines and acetylcholine, albeit to different extents than MAH cells. Both MAH cells and their nonimmortal counterparts are able to increase slightly their cholinergic function upon short-term exposure to CDF/LIF, a factor known to induce acetylcholine synthesis in postmitotic sympathetic neurons. Taken together, these data suggest that progenitor cells in the sympathoadrenal lineage acquire the ability to simultaneously transcribe several different neurotransmitter enzyme genes early in development, prior to their choice of final cell fate. At the same time, the progenitors possess receptors which regulate expression of these genes in response to environmental factors. This ability may permit the cells to choose from several different transmitter phenotypes in response to different environments, as they migrate through the embryo. The persistent transcription of these genes in adult cells, moreover, may in part account for the phenotypic plasticity of cells in this lineage.
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PMID:Co-expression of multiple neurotransmitter enzyme genes in normal and immortalized sympathoadrenal progenitor cells. 168 90

Following removal of the presynaptic input to the superior cervical ganglion (SCG) of the neonatal rat, there is an increase in substance P (Kessler et al.: Science 214:335-336, 1981; Kessler and Black: Brain Res 234:182-187, 1982) and the mRNA coding for its prohormone precursor (Roach et al.: Proc Natl Acad Sci USA 84:5078-5081, 1987). However, the functional significance of this increase has been unclear. We report here that SP increases dramatically in cultures of SCG grown in the presence of conditioned medium from con-A-stimulated splenocytes. The effect is mimicked by growing SCG explants in the presence of human recombinant interleukin-1 (hrIL-1) but not hrIL-2. Nerve growth factor (NGF) is not involved in mediating this effect since antibodies to NGF included in the culture fail to alter the lymphokine-induced increase in SP. Moreover, the effect is somewhat specific for SP since the activities of tyrosine hydroxylase, tryptophan hydroxylase, and choline acetyltransferase (enzymes in the biosynthetic pathways for norepinephrine, serotonin, and acetylcholine) are not similarly elevated. Dorsal root ganglia respond with only modest increases in SP. The action of lymphokines in stimulating SP may, therefore, be a ganglion-specific action in promoting recovery following injury.
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PMID:Conditioned medium from activated splenocytes increases substance P in sympathetic ganglia. 169 49

The mouse tryptophan hydroxylase gene was isolated and its intron/exon boundaries and putative regulatory sequences identified. To isolate the gene a mouse mastocytoma cDNA clone encoding tryptophan hydroxylase was used to identify and isolate ten overlapping DNA fragments from a mouse genomic library. Restriction mapping and sequence analysis of the clones revealed that the gene contains 11 exons and covers a region of DNA of approximately 21 kb. The transcription initiation site was mapped and the major site of initiation yields an untranslated leader sequence of 124 nucleotides. A minor initiation site is located 9 nucleotides 3' of the major site. The 5' untranslated sequence is interrupted by the first intron. Analysis of the sequence upstream of the initiation site showed the presence of several putative promoter and regulatory sequences. Nine of the ten intron/exon boundaries of tryptophan hydroxylase are conserved with tyrosine hydroxylase and phenylalanine hydroxylase, further delineating the evolutionary relationship of these three genes.
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PMID:Isolation and structural characterization of the murine tryptophan hydroxylase gene. 171 8

The distribution, morphology and number of serotonin-, catecholamine- and substance P-containing neurons in the human dorsal raphe nucleus were studied. Parallel series of sections were prepared from 10 human brainstems obtained at autopsy from patients without neurological disease aged between 42 and 88 years. The neurons were identified using immunohistochemistry with antibodies raised against phenylalanine hydroxylase (tryptophan hydroxylase-containing, serotonin neurons), tyrosine hydroxylase (catecholamine neurons) and substance P. A reference series of Nissl-stained sections was also prepared and data published separately were used to delineate the subnuclear divisions of the dorsal raphe nucleus and to establish the total number of neurons in each subnucleus. The following principal findings emerged. (1) Serotonin-synthesizing neurons are present in all regions of the dorsal raphe nucleus and their total number is 165,000 +/- 34,000. The same types of neurons as those seen in Nissl material characterize each of the five subnuclei (caudal, dorsal, ventral, ventrolateral and interfascicular). (2) Substance P-containing neurons mostly occupy the rostral part of the nucleus and their number is 74,600 +/- 17,600. (3) Catecholamine cells are only found in the rostral part of the dorsal raphe nucleus and their number is 5600 +/- 3400. (4) In the ventral and interfascicular subnuclei the combined number of serotonin-synthesizing and substance P-containing neurons exceeds the total number of Nissl-stained neurons suggesting that serotonin and substance P co-exist in a substantial part of the cell population of the dorsal raphe nucleus. This is further supported by the highly similar morphology and size of these neurons. It is concluded that there are demonstrable chemical differences between the various subregions of the human dorsal raphe nucleus. These differences are in harmony with the results of hodological studies in animals, which have demonstrated differential projection pathways emerging from this nucleus.
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PMID:Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus. 172 Feb 27

Cloning full length cDNAs is a difficult task especially if mRNAs are not abundant or if tissue is only available in limited amounts. Current strategies are based on in vitro amplification of cDNAs after adding a homopolymeric tail at the 3' end of the ss-cDNA. Since subsequent amplification steps yield unspecific amplified DNA mostly due to non-specific annealing of the reverse primer containing a homopolymeric tail, we have devised a new strategy based on the ligation of single-stranded oligodeoxyribonucleotide to the 3' end of single-stranded cDNAs. The efficiency of the strategy was assessed by analyzing the 5' ends of the rat pineal gland tryptophan hydroxylase messenger. The 5' end of the least abundant messenger (0.005% of total mRNAs) could be cloned without selection. Sixty percent of the analyzed clones correspond to TPH. This technique revealed a 5-nt stretch not apparent using dG tailing strategy. The potentiality of the method for generating cDNAs libraries was tested with 10(4) PC12 cells. In this library, the abundance of tyrosine hydroxylase clones (0.03%) correlated well with the abundance of the corresponding messenger, showing that no major distortion was introduced into the construction of the library.
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PMID:Oligodeoxyribonucleotide ligation to single-stranded cDNAs: a new tool for cloning 5' ends of mRNAs and for constructing cDNA libraries by in vitro amplification. 192 6

The application of high-performance liquid chromatography to the study of biogenic amine-related enzymes is reviewed. Biogenic amines include catecholamines (dopamine, norepinephrine and epinephrine), indoleamines (serotonin and melatonin), imidazoleamines (histamine), polyamines (putrescine, spermidine and spermine) and acetylcholine. Three particular aspects are covered. The first aspect is the assay of enzyme activities of biogenic amine-related enzymes, such as tyrosine hydroxylase, tryptophan hydroxylase, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase. The introduction of highly sensitive assays of biogenic amines with electrochemical detection or fluorescence detection have made possible the non-isotopic assay of these activities, replacing the previously used radioisotopic methods. The second aspect is the purification of these enzymes. Since biogenic amine-synthesizing enzymes are generally unstable, rapid and efficient purification of these enzymes is very useful. The third aspect is the assay of biogenic amines (for example, acetylcholine and polyamines) using post-column derivatization with biogenic amine oxidases and electrochemical detection.
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PMID:Application of high-performance liquid chromatography to the study of biogenic amine-related enzymes. 193 43


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