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)

We sought to determine, in rat embryo, when and at what site in their migration cells derived from the neural crest differentiate into sympathetic neuroblasts. This has been accomplished by immunocytochemical detection, within the cells, of the enzymes catalyzing catecholamine biosynthesis-tyrosine hydroxylase [TH; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] dopamine-beta-hydroxylase [DBH; 3,4-dihydroxyphenylethylamine,ascorbate:oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1)]-and, as a marker of prospective adrenal medullary cells, the enzyme phenylethanolamine N-methyltransferase (PNMT; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28). TH and DBH, not detected in the neural crest, appear almost simultaneously in cells of the thoracic sympathetic ganglia in 11-day-old embryos, and in abdominal and lumbar ganglia 1-2 days later, thereby exhibiting a characteristic rostral-caudal gradient of differentiation. Cells stained for TH and DBH are seen in the gut wall from day 11 to day 14, but not thereafter. Cells stained for TH and DBH appear in the adrenal anlage at day 15. However, PNMT is not detected in the adrenal until day 17 of development, and is present only in the sympathoblasts in contact with the adrenal cortex. Treatment of pregnant rats with dexamethasone failed to accelerate the appearance of PNMT in the embryo or to initiate its expression in cells of other sympathetic organs. We conclude that neural crest cells express a noradrenergic phenotype only after leaving the neural crest and that these cells are labile with respect to their neurotransmitter and are capable of transformation in response to environmental stimuli.
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PMID:Appearance of catecholamine-synthesizing enzymes during development of rat sympathetic nervous system: possible role of tissue environment. 3 53

Antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in norepinephrine synthesis) and dopamine beta-hydroxylase (DBH, the last enzyme in the synthesis) were used for immunohistochemical staining of human brain locus coeruleus sections, obtained postmortem from suicide victims and matched controls. Stain density over individual cells was quantified by a computerized, video-camera-based image analysis system. Mean stain density for TH was significantly lower (by about 30%) in the locus coeruleus of suicide victims. There was no difference between suicides and controls in DBH immunoreactivity or in the number of TH immunoreactive cells. Reduced TH availability, either genetically or environmentally determined, may contribute to the noradrenergic insufficiency postulated to occur in depression and the increased beta-adrenergic receptor concentrations observed in prefrontal cortex of suicide victims.
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PMID:Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims. 134 45

Catecholamine neurotransmitters--dopamine, noradrenaline (norepinephrine), adrenaline (epinephrine)--are synthesized in catecholaminergic neurons from tyrosine, via dopa, dopamine and noradrenaline, to adrenaline. Four enzymes are involved in the biosynthesis of adrenaline: (1) tyrosine 3-mono-oxygenase (tyrosine hydroxylase, TH); (2) aromatic L-amino acid decarboxylase (AADC, or DOPA decarboxylase, DDC); (3) dopamine beta-mono-oxygenase (dopamine beta-hydroxylase, DBH); and (4) noradrenaline N-methyltransferase (phenylethanolamine N-methyltransferase, PNMT). We cloned full-length complementary DNAs (cDNAs) and genomic DNAs of human catecholamine-synthesizing enzymes (TH, AADC, DBH, PNMT) and determined the nucleotide sequences and the deduced amino acid sequences. We discovered multiple messenger RNAs (mRNAs) of human TH, human DBH, and human PNMT. Four types (types 1, 2, 3, and 4) of human TH mRNAs are produced by alternative mRNA splicing mechanism from a single gene. We found the multiple forms of TH in two species of monkeys, but only a single mRNA corresponding to human TH type 1 in Sunkus murinus and rat, suggesting that the multiplicity of TH mRNA is primate-specific. Total TH mRNA, especially the most abundant type 2 and type 1 mRNAs in the human brain, were found to be reduced during the process of aging. The multiple forms of human TH may give additional regulation to the human enzyme, probably through altered phosphorylation and activation. We have succeeded in producing transgenic mice carrying multiple copies of the human TH gene in brain and adrenal medulla. The level of human TH mRNA in brain was about 50-fold higher than that of endogenous mouse TH mRNA. In situ hybridization demonstrated an enormous region-specific expression of the transgene in substantia nigra and ventral tegmental area. TH immunoreactivity in these regions, Western blot analysis, and TH activity measurements proved definitely increased TH in transgenic mice, though not comparable to the increment of the mRNA. However, catecholamine levels in transgenics were not significantly different from those in non-transgenics. The results suggest complex regulatory mechanisms for human TH gene expression and for the catecholamine levels in transgenic mice. Kohsaka and Uchida in collaboration with us applied genetically engineered (human TH cDNA-transfected) non-neuronal cells to brain tissue transplantation in parkinsonian rat models. We isolated and sequenced a full-length cDNA encoding human AADC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genes for human catecholamine-synthesizing enzymes. 168 50

Immunohistochemical properties of the terminal nerve network in the rat heart were assessed by use of the elution-restaining method. The colocalization of the enzymes involved in catecholamine synthesis (tyrosine hydroxylase--TH. dopamine-beta-hydroxylase--DBH) as well as the respective distributions of the neuropeptides associated with the adrenergic nervous system (neuropeptide tyrosine--NPY, C-terminal flanking peptide of neuropeptide Y--C-PON) were studied in series of serial sections throughout the interatrial septum and the atrioventricular junction. Our data suggest that ganglion cells of sulcus terminalis as well as the epicardial ganglia enclosed between the superior vena cava and ascending aorta are VIP- and TH-negative, but neuropeptide Y- and DBH-immunoreactive. They give rise to three intraseptal nerves directed towards the specialised structures of the atrioventricular junction. These nerve fascicles contain abundant, thick TH-immunoreactive nerve fibres and scarce, thin NPY- and DBH-immunoreactive fibres. The cell bodies of the intramural ganglion cells localized between the right and left branches of the bundle of His (Moravec and Moravec 1984) are strongly TH- and DBH-immunoreactive. They are innervated by thick nerve fibres having the same immunohistochemical properties (NPY- and DBH-immunoreactivities) as those of a subpopulation of the epicardial ganglion cells and seem to supply some of the TH-immunoreactive nerve fibres directed via the intraseptal nerves to the epicardial ganglia. The existence of a multicomponent nerve network, characterized by a reciprocal innervation of the sinus node and atrioventricular node areas, is suggested by our immunohistochemical data.
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PMID:Catecholaminergic and peptidergic nerve components of intramural ganglia in the rat heart. An immunohistochemical study. 170 21

Recently we reported that the anteroventral periventricular nucleus (AVPv) of the preoptic region contains a dramatic sexual dimorphism in the distribution of tyrosine hydroxylase-(TH-)immunoreactive cells and fibers in the rat. This sexual dimorphism appears to be due to a greater density of dopaminergic fibers, and a larger number of dopaminergic cell bodies, in the AVPv of the female. In the present study we used an indirect immunohistochemical method to evaluate the distribution of TH-immunoreactive cell bodies and fibers, and of dopamine-beta-hydroxylase-(DBH-)stained fibers, in the AVPv of female rats that were treated with testosterone propionate (TP) perinatally or postnatally, or were left untreated. All of the postnatally TP-treated animals failed to show a phasic pattern of luteinizing hormone (LH) secretion in response to estrogen and progesterone injections. Both the perinatally and postnatally TP-treated females had polyfollicular ovaries that lacked corpora lutea at the time of gonadectomy. Perinatal TP exposure resulted in what appears to be a complete masculinization of both the number of TH-stained cells and the density of TH-stained fibers in the AVPv. The number of TH-stained cells in the postnatally TP-treated females was also completely masculinized, although the density of TH-stained fibers did not appear to be altered significantly. Gonadectomy resulted in a moderate increase in the density of TH-stained fibers in adult males, and did not significantly affect the fiber density in females, or the number of TH-stained cells in either sex. The distribution of DBH-stained fibers in the AVPv did not appear to be altered in any of the treatment groups. These results suggest that the distribution of dopaminergic fibers in the AVPv may be sensitive to testosterone levels in the adult male, and that although the critical period for the development of this fiber distribution may begin in the prenatal period, the number of dopaminergic cells in the AVPv can be completely sex reversed by a single postnatal dose of TP that appears to correlate with a permanent disruption of the normal pattern of gonadotropin secretion.
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PMID:Influence of perinatal androgen on the sexually dimorphic distribution of tyrosine hydroxylase-immunoreactive cells and fibers in the anteroventral periventricular nucleus of the rat. 286 81

Parasympathetic neurons of the ciliary ganglion are innervated by preganglionic cholinergic neurons whose cell bodies lie in the brain stem; the ganglion cells in turn provide cholinergic innervation to the intrinsic muscles of the eye. Noradrenergic innervation of the iris is supplied by sympathetic neurons of the superior cervical ganglion. Using immunocytochemical and histochemical techniques, we have examined the ciliary ganglion of adult rats for the expression of cholinergic and noradrenergic properties. As expected, the postganglionic ciliary neurons possessed detectable levels of choline acetyltransferase immunoreactivity (ChAT-IR). Unexpectedly, many ciliary neurons also exhibited immunoreactivity for tyrosine hydroxylase (TH-IR). Some had dopamine beta-hydroxylase-like (DBH-IR) immunoreactivity, but none contained detectable catecholamines, even after treatment with nialamide and L-DOPA. A sparse plexus of fibers exhibiting faint TH-IR was present in the irises of acutely sympathectomized rats. The terminals of preganglionic axons in the ciliary ganglion exhibited not only immunoreactivity for ChAT, but also for TH and contained stores of endogenous catecholamine. Neither ciliary neurons nor their preganglionic innervation accumulated detectable stores of exogenous catecholamines. Rats sympathectomized as neonates by treatment with 6-hydroxydopamine subsequently had a greater proportion of neurons possessing detectable TH-IR in the ciliary ganglion; both the TH-IR perikarya and their axons in the iris were more intensely immunofluorescent. TH-IR was present in the ciliary neuron cell bodies of mouse, guinea pig, and ferret. These species, however, lacked detectable TH-IR or catecholamine stores in preganglionic terminals. These observations indicate that mature, functionally cholinergic neurons from 2 different embryonic origins, postganglionic ciliary neurons derived from the neural crest and preganglionic neurons derived from the neural tube, display several catecholaminergic properties.
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PMID:Catecholaminergic properties of cholinergic neurons and synapses in adult rat ciliary ganglion. 289 Jul 21

The neurotransmitters used by the sensory neurones of the dorsal root ganglia (DRG) are unknown. A proportion of these cells contain physiologically active peptides; for example, subpopulations of small-diameter neurones contain substance P or somatostatin. Although these peptides probably have some influence on synaptic transmission in the dorsal horn of the spinal cord, their status as neurotransmitters is uncertain and it is possible that they coexist with conventional neurotransmitters. In addition, the neurones containing identified peptides account for only a fraction of the DRG sensory neurones. There is evidence that the DRG contain catecholamines within fibres thought to be autonomic, but these substances have not been found within the sensory cell bodies themselves. Moreover, the apparently inappropriate, inhibitory physiological effect of catecholamines in the dorsal horn has argued against their being primary sensory neurotransmitter molecules. We have used here antisera against tyrosine hydroxylase (TH; EC 1.14.16.2) and dopamine-beta-hydroxylase (DBH; EC 1.14.17.1), two enzymes specific to catecholaminergic cells, to show that a subpopulation of rat DRG neurones is catecholaminergic and that the neurotransmitter they make is probably dopamine. We believe this to be the first report of catecholaminergic sensory neurones.
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PMID:A subpopulation of rat dorsal root ganglion neurones is catecholaminergic. 613 Apr 74

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.
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PMID:Increased adrenal catecholamines in salt-sensitive genetically hypertensive Dahl rats. 613 26

We describe the transient expression of catecholaminergic traits in cranial sensory and dorsal root ganglia of the embryonic rat in vivo. Isolated cells expressing tyrosine hydroxylase (T-OH) immunoreactivity were initially detected in trigeminal (V) ganglion anlages as early as gestational Day 10.5 (E10.5; 18-22 somites). Neurofilament (NF) protein was also evident in V at these early stages. By E11.5 (27-30 somites) clusters of T-OH-positive cells were visible in V. Many of these cells were bipolar; others sent processes into the primitive brainstem. In addition, cells expressing T-OH were apparent in primordia of sensory ganglia serving the glossopharyngeal (IX) and vagal (X) cranial nerves. By this stage (E11.5) all cranial sensory ganglia were rich in NF protein, but immunoreactivity was confined to cellular processes rather than perikarya. By E12 (35-37 somites), only a few, faintly positive T-OH-containing cells were evident in V. However, DBH- and T-OH-positive cells were visible within the more caudal nodose and petrosal ganglia. Furthermore, isolated bipolar cells expressing T-OH were detected in rostral dorsal root ganglia at this stage. Catecholamine fluorescence could not be detected in any sensory ganglia even after maternal treatment with inhibitors of monoamine oxidase. Catecholaminergic cells were not seen at any stage in anlages of the acousticovestibular nucleus. Immunoreactive T-OH was undetectable in all ganglia by E13.5 (46-48 somites). These findings highlight the fact that transient expression of the catecholamine phenotype during development is a widespread phenomenon, evident in a variety of cell types of diverse embryonic origin.
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PMID:Transient expression of selected catecholaminergic traits in cranial sensory and dorsal root ganglia of the embryonic rat. 614 Nov 17

Using a double labeling immunohistochemical method with antibodies to tyrosine hydroxylase and dopamine-beta-hydroxylase, we reexamined the topographical distribution of dopaminergic (DA) and noradrenergic (NA) cells in the pons-mesencephalon junction of the cat. Besides DA cells of SN and its extensions, DA cells were also observed more caudally in nucleus raphe linearis intermedius and dorsalis, decussation of brachium conjunctivum, fasciculus longitudinalis medialis and periaqueductal gray. In nucleus locus coeruleus, cells exhibited variable levels of DBH, but dopaminergic cells were not evidenced in this structure.
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PMID:Identification of catecholamine cell bodies in the pons and pons-mesencephalon junction of the cat brain, using tyrosine hydroxylase and dopamine-beta-hydroxylase immunohistochemistry. 614 89


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