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)

Intrastriatal transplantation of fetal striatal (STR), cortical (CTX), or ventral mesencephalic (VM) tissue into the normal striatum has been shown to produce behavioral deficits (38). Here, we have examined the cellular elements of the transplants and their connectivity with the host using histochemistry for cytochrome oxidase (CO) and acetylcholinesterase (AChE), immunocytochemistry for glial fibrillary acidic protein (GFAP), OX42, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), serotonin (5-HT), and cholecystokinin (CCK). Autoradiography for dopamine D1 and D2, muscarinic cholinergic, and serotonin 5-HT1 and 5-HT2 receptors at 5-15 months after transplantation was also investigated. CO staining showed that all transplants were metabolically active. The STR and VM transplants contained AChE-positive neurons and fibers. The CTX transplants exhibited AChE terminals with an appearance similar to that of the host cortex. AChE staining within the STR transplants was patchy. 5-HT-, TH-, and DBH-immunoreactive (IR) fibers were found in the STR and CTX transplants. In two of six CTX transplants, many TH-IR neurons were present. The VM transplants contained many TH-IR, 5-HT-IR, and DBH-IR cell bodies and fibers. CCK-IR stain was found in the VM transplant and was coextensive with regions containing TH-IR cell bodies. Fibers stained by all markers crossed the transplant and host border. Receptor autoradiography revealed that muscarinic cholinergic and 5-HT2 receptors were present in the STR, CTX, and VM transplants. In addition, dopamine D1 and D2 receptors were present in the STR transplants. Intermittent heavy staining for GFAP and OX42 were observed along the border of most transplants and the hosts. It was noted that high densities and hypertrophy of GFAP- or OX42-stained astrocytes or microglia, respectively, were present in the transplants and adjacent host. OX42-stained macrophages were found in many transplants. The present results indicate that intrastriatal transplants into the intact normal brain express numerous histochemical, immunocytochemical, and receptor features characteristic of the appropriate adult tissues. The afferents from the host extend into the STR and CTX transplants, and neural fibers from the VM transplants grew into surrounding host tissue, suggesting possible anatomical connection. Ultrastructural evidence is needed to determine if these fibers form synaptic connections. The results from GFAP and OX42 immunocytochemical staining support the possibility suggested by behavioral studies that damage to the host brain is induced by neural transplantation.
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PMID:Striatal, ventral mesencephalic and cortical transplants into the intact rat striatum: a neuroanatomical study. 165 Dec 54

To determine the portion of ganglionic dopamine stored in the small intensely fluorescent (SIF) cells of the superior cervical ganglion, rats were treated chronically with the neurotoxin guanethidine (50 mg/kg i.p. daily for 6, 13 or 18 days) which destroys noradrenergic neurons. The guanethidine effect was assessed in the ganglion using biochemistry of dopamine and norepinephrine and immunocytochemistry of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). After 18 days of treatment, the ganglionic norepinephrine content was reduced by 80%, but the dopamine content was reduced by only 20%. Morphologic analysis of ganglia stained to distinguish noradrenergic neurons (TH positive, DBH positive) and SIF cells (TH positive, DBH negative) indicated that guanethidine treatment reduced the number of noradrenergic neurons by 70%, dropping from 19413 +/- 1402 to 6515 +/- 1296 per ganglion, but increased the number of dopaminergic SIF cells by 80% from 578 +/- 150 to 1056 +/- 151 per ganglion. Based on these findings, it is concluded that a substantial portion of the dopamine in the rat superior cervical ganglion is located outside the noradrenergic neurons, i.e. in the SIF cells. Extrapolating the data obtained using guanethidine versus control rat leads to infer that although the proportion of SIF cells in the superior cervical ganglion is small (3 +/- 1% of the SIF and noradrenergic neurons combined), about 40% of the total ganglionic dopamine resides in SIF cells, with the remainder serving as precursor in noradrenergic neurons.
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PMID:Effect of guanethidine on dopamine in small intensely fluorescent cells of the superior cervical ganglion of the rat. 167 96

The expression of dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) immunoreactivity (IR) after short-term (2 days) and long-term (3 weeks) sympathectomy was investigated in rat cerebral vessels, dura mater and pterygopalatine ganglion neurones (which are known to project to cerebral arteries) by immunohistochemistry at both the light and electron microscopical levels. TH-IR, like glyoxylic acid-induced fluorescence, was completely abolished by sympathectomy. By contrast, DBH-IR was localized in nerve fibres, lacking 5-hydroxydopamine (5-OHDA)-labelled vesicles, along cerebral vessels of long-term sympathectomized rats, but not in the dura mater, and in pterygopalatine ganglia, where the number of DBH-IR neurons increased from 27.87% to 54.11%. Since virtually all the pterygopalatine neurons displayed choline acetyltransferase (ChAT)-IR, both in control and sympathectomized rats, it is concluded that long-term sympathectomy caused an increase of the expression of DBH-IR in cholinergic neurones of the pterygopalatine ganglion, without these neurons producing or storing noradrenaline.
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PMID:Increase of dopamine beta-hydroxylase immunoreactivity in non-noradrenergic nerves of rat cerebral arteries following long-term sympathectomy. 167 22

This light microscopic immunohistochemical study investigates the distribution and target interrelations of nerve fibers in bronchus-associated lymphoid tissues (BALT) of rat and cat by using antisera against (1) the polyneuronal marker protein gene product 9.5 (PGP 9.5), (2) selected opioid and nonopioid peptides, and (3) the marker enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). In both species, a similar distribution pattern of PGP, peptide, and catecholamine enzyme immunoreactive was observed. Anti-PGP 9.5 stained all nerve fibers (except some smaller, calcitonin gene-related peptide-immunoreactive (CGRP-ir) fibers presumably of the C-type) throughout the different compartments of BALT, e.g., under the epithelium, in the smooth muscle layer, along the vasculature, and between immune cells of BALT parenchyma. The distribution of fibers staining for peptides (substance P (SP), (CGRP), neuropeptide Y (NPY). Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu) and/or the catecholamine enzymes was also not compartment-specific. However, the density of the different peptidergic fibers and those staining for the marker enzymes exhibited region- and target-specific variations, e.g., fibers, cocontaining substance P and CGRP were more ubiquitous in nonvascular regions than codistributed NPY-, TH-, and DBH-ir fibers, which clearly prevailed in perivascular plexus. Regularly, nerve fibers staining for any of the peptides and markers investigated formed close contacts with mast cells, cells of the macrophage/monocyte cell line (identified as ED1 + cells), and/or other lymphoid cells, although with different frequencies. We assume that the SP/CGRP innervation is mainly of primary sensory origin, while the NPY innervation is chiefly derived from postganglionic noradrenergic sympathetic neurons. The VIP/PHI component is most likely postganglionic cholinergic while the opioid component, apparently derived from the Proenkephalin precursor, could be of differential origin. We propose that the neuroimmune connections in BALT play a significant role in the regulation and/or modulation of physiological/pathophysiological mechanisms of the lung. BALT may also be an integral part of the psycho-neuro-immune axis.
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PMID:The neuroimmune link in the bronchus-associated lymphoid tissue (BALT) of cat and rat: peptides and neural markers. 167 20

In the present immunohistochemical study, the distribution of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in the larynx was examined and compared with that of fibers containing tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), and with that of acetylcholinesterase (AChE)-positive nerve fibers, in intact and vagotomized rats and in rats subjected to removal of the superior cervical ganglion (SCG). Fibers showing TH/DBH-like immunoreactivity (LI) were only found in the walls of arteries and arterioles, whereas AChE-positive nerve fibers were located close to the acini and ducts of the glands, in blood vessel walls, in the perichondrium and in the lamina propria. NPY-LI and VIP-LI coexisted in local AChE-positive ganglionic cells and in a subpopulation of the AChE-positive fibers, NPY-LI also being present in some periarterial fibers showing TH/DBH-LI. Unilateral removal of the SCG eliminated the TH/DBH-innervation in the upper but not the lower parts of the larynx ipsilaterally, whereas the NPY-innervation of the arteries in the upper parts only partly disappeared and the NPY-innervation of the other structures remained unchanged. The distribution of VIP-innervation was unchanged after vagotomy and removal of the SCG. The results suggest that VIP is present in the postganglionic parasympathetic innervation, whereas NPY is present in both the postganglionic parasympathetic and sympathetic innervation of the rat larynx.
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PMID:Studies on colocalization of neuropeptide Y, vasoactive intestinal polypeptide, catecholamine-synthesizing enzymes and acetylcholinesterase in the larynx of the rat. 167 88

The vestibular sympathetic fibers were examined in 20 guinea pigs by immunohistochemical demonstration of tyrosine hydroxylase and dopamine beta-hydroxylase. The vestibular sympathetics originated in the ipsilateral superior cervical ganglion and entered the internal auditory meatus along the labyrinthine artery. At the Schwann-glial border, some of the sympathetic fibers left the artery and went into both the superior and inferior divisions of the vestibular nerves and made a loose mesh-work among the Scarpa's ganglion cells while other fibers followed the labyrinthine artery. Both types of fibers entered the crista ampularis and otoconial macula after several bifurcations in the cribrosa and terminated either near the capillaries beneath the sensory epithelial or among the vestibular nerve fibers. These fibers traveled freely in the vestibular labyrinth and were not restricted to following blood vessels or vestibular nerve fibers. Some sympathetic fibers made direct contact with the vestibular efferent fibers or the vestibular afferent fibers at the node of Ranvier. Sympathetic fibers were not observed in the sensory epithelia and semicircular canals and were rarely found in the vicinity of the dark cells: however, they were found to be distributed in the endolymphatic sac.
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PMID:Vestibular sympathetic nervous system in guinea pig. 168 76

This study was designed to determine the effect of neonatally-produced hypothyroidism on reserpine-elicited tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (D beta H) induction in the superior cervical ganglion (SCG) in rats. Some rats were rendered hypothyroid from birth by daily treatment with propylthiouracil (PTU). Some hypothyroid rats received replacement therapy with triiodothyronine (T3). Some rats received PTU for 20 days, beginning at 90 days of age. Some rats were not treated and served as controls. TH and D beta H activities were assayed at 30, 50 and 110 days of age. Basal TH activity in the SCG for rats made hypothyroid as neonates was significantly lower than for controls at all ages tested; basal D beta H activity for these rats was lower than for controls at 30 and 50 days of age, but by 110 days was not different from that for controls. Basal TH activity for rats made hypothyroid as adults was intermediate between that for controls and rats made hypothyroid from infancy. Injecting control rats with reserpine produces a robust TH induction in the SCG at each age tested, and a strong D beta H induction at 50 and 110 days of age. Reserpine-evoked TH and D beta H inductions in rats made hypothyroid as adults were not different from those seen in controls. In contrast, rats made hypothyroid from infancy showed virtually no evidence of a reserpine-provoked TH or D beta H induction at any age tested. TH and D beta H inductions for hypothyroid rats given T3 replacement were completely normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine hydroxylase and dopamine beta-hydroxylase inductions evoked by reserpine in the superior cervical ganglion of developing eu- and hypothyroid rats. 168 70

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

Expression of neurotransmitter phenotype during development of the nervous system is determined by several micro-environmental factors including cell aggregation. In order to delineate the role of cell aggregation and nerve growth factor (NGF) in regulating catecholamine expression, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) mRNA levels were examined in PC12 cells at different cell densities with and without NGF treatment. Upon plating of PC12 cells from low density (0.3-1.0 x 10(5) cells/cm2) to high density (0.5-2.0 x 10(6) cells/cm2) TH mRNA levels increased 4-fold within 1 day and remained at this level for several days. In cells replated from high to low density, TH mRNA returned to original levels within 1 day. In addition to TH mRNA, TH protein and dopamine levels were also found to increase in high-density cultures. In contrast to the increase in TH mRNA, DBH mRNA decreased about 40% in cells plated from low to high density. Hence, cell density differentially regulated TH and DBH mRNA levels. Unlike cell density, NGF treatment led to a decrease in both TH and DBH mRNA levels. However, when NGF treated cells were replated from low to high density, TH and dopamine levels increased. Thus NGF did not alter the density dependent regulation of TH. Similarly, TH mRNA levels increased in F4 cells, a mutant PC12 cell line unresponsive to NGF, when plated from low to high density. DBH mRNA decreased to undetectable levels when NGF treated PC12 cells were plated to high density, demonstrating a synergetic effect of cell density and NGF treatment on DBH mRNA levels.
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PMID:The differential effects of cell density and NGF on the expression of tyrosine hydroxylase and dopamine beta-hydroxylase in PC12 cells. 168 6

We have measured levels of mRNA coding for the catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H), phenylethanolamine N-methyltransferase (PNMT) and for neuropeptide Y (NPY) in rat adrenal medulla by using in situ hybridization histochemistry. Ages of one day before birth (E21), 12 h, 24 h, 2 days and 4 days after birth and in adults were studied. TH, D beta H and NPY mRNA levels increased markedly postnatally. Twelve hours after birth the levels of mRNA for TH, D beta H and NPY were, respectively, 512 +/- 18%, 370 +/- 24% and 253 +/- 21% of E21 levels. At 24 h of age NPY mRNA level was 437 +/- 73% of fetal value. In contrast, the levels of mRNA coding for PNMT increased more slowly and reached 196 +/- 9% of E21 level on postnatal day four and was further increased in adult rats.
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PMID:Changes in levels of mRNA coding for catecholamine synthesizing enzymes and neuropeptide Y in the adrenal medulla of the newborn rat. 168 39


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