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.
 ...
PMID:Appearance of catecholamine-synthesizing enzymes during development of rat sympathetic nervous system: possible role of tissue environment. 3 53

Neuropeptide FF (NFF) is an amidated octapeptide of bovine origin. It has some antiopioid-like effects and it elevates blood pressure when injected intravenously in rats. NFF-immunoreactive nerve cells and terminals are localized in large numbers in the dorsomedial caudal brainstem which is a region involved in central regulation of blood pressure. We compared the localization of NFF-immunoreactive neurons with medullary catecholamine-synthesizing neurons by using immunohistochemical double-labeling and light microscopic mirror methods. NFF and tyrosine hydroxylase coexisted in a minor portion of the NFF neurons in the nucleus of the solitary tract and occasional cell bodies were stained with both NFF and PNMT (phenylethanolamine N-methyltransferase) antisera. The results have anatomical correlation with previous pharmacological reports, suggesting that NFF is present in neuronal systems involved in cardiovascular reflex arcs.
 ...
PMID:Neuropeptide FF is colocalized with catecholamine-synthesizing enzymes in neurons of the nucleus of the solitary tract. 135 74

Cell adhesion molecules play a major role in determining tissue architecture during histogenesis. This immunocytochemical study of the adrenal gland examines the embryonic and early postnatal cellular expression of two neural cell adhesion molecules, NCAM and L1, which are widely expressed in brain and have been found also to be expressed in the adult rat adrenal gland. In parallel, antibodies directed against two neuroendocrine cell markers, tyrosine hydroxylase and phenylethanolamine N-methyltransferase, were employed to verify the phenotypic nature of developing chromaffin cells in order to correlate cell adhesion molecule expression with the state of chromaffin cell differentiation. NCAM was found to be expressed by chromoblasts within extra-adrenal blastema (i.e. before their migration into the cortical primordium) at the 16th day of embryonic life. It continued to be expressed by all developing chromaffin cells after their infiltration into the developing adrenal gland at all ages. L1 was also expressed by chromoblasts in extra-adrenal sites, but was found only in a subpopulation of chromaffin cells within the cortical primordium from the 16th embryonic day onwards. Those chromoblasts which expressed L1 constituted relatively large compact cell clusters within the gland at this stage, while intra-adrenal chromaffin cells not expressing L1 were dispersed in small cell groups. L1 was also strongly expressed by nerve fibres (and their surrounding Schwann cells) which appeared to innervate cell groups as early as the 16th embryonic day. Both extra- and intra-adrenal chromoblasts expressed tyrosine hydroxylase, but the large L1-positive cell aggregates were less intensely immunoreactive for tyrosine hydroxylase than were cells in small groups. PNMT expression was restricted to L1-negative intra-adrenal chromoblasts present in small groups. Ultrastructural observations demonstrated that cells expressing L1 contained few secretory granules at the 18th embryonic day. It is concluded from these data that these chromoblasts are the precursors of the noradrenergic cells found in the mature gland. In addition, the arrangement of noradrenergic chromaffin cells in the form of homotypic cell groups throughout the course of histogenesis of the adrenal medulla is likely to be a direct consequence of the exclusive co-expression of both NCAM and L1 by this subpopulation of maturing chromaffin cells.
 ...
PMID:Expression of cell adhesion molecules and catecholamine synthesizing enzymes in the developing rat adrenal gland. 136 84

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)
 ...
PMID:Genes for human catecholamine-synthesizing enzymes. 168 50

Following the iontophoretic deposition of Phaseolus vulgaris leucoagglutinin (PHA-L) into the rostral ventrolateral medulla (RVL), two-color immunoperoxidase staining was employed to demonstrate contiguity between PHA-L-immunoreactive (PHA-LI) varicose fibers and boutons and brainstem monoaminergic cells. Black-stained PHA-LI cells in the deposition site were found to be located among amber-stained phenylethanolamine N-methyl transferase-immunoreactive (PNMT-I) neurons of the C1 cell group. RVL projections were contiguous with PNMT-I neurons of the C1, C2 and C3 cell groups, with tyrosine hydroxylase-immunoreactive (TH-I) neurons of the A1, A2 and A5 cell groups, and with serotonin-immunoreactive (5-HT-I) neurons of the B1, B2 and B3 cell groups. Preliminary findings of this study have been presented previously (Soc. Neurosci. Abstr., 15 (1989) 451).
 ...
PMID:Projections from the rostral ventrolateral medulla to brainstem monoamine neurons in the rat. 205 40

Substance P (SP) and catecholamines, particularly adrenaline, have been implicated in cardiovascular responses mediated by neurons in the rostral ventrolateral medulla (RVL). Immunoperoxidase labeling of an antiserum against SP and/or immunoautoradiographic localization of catecholamine (tyrosine hydroxylase-TH)- or adrenaline (phenylethanolamine N-methyltransferase-PNMT)-synthesizing enzymes were examined histologically to determine the cellular basis for a functional interaction involving either synaptic or intracellular relations between these putative transmitters in the adult rat RVL. Peroxidase labeling for SP was localized in perikarya, dendrites, and axon terminals. Most of these perikarya were located medial and ventral to those labeled with TH or PNMT within the same section. However, as others have previously demonstrated by light microscopy, colocalization of SP-like immunoreactivity (SPLI) and PNMT was seen in a few perikarya of colchicine treated animals. Both single- and dual-labeled perikarya contained abundant dense core vesicles. The terminals with SPLI were 0.4-1.4 micron in diameter and contained a few mitochondria, a large population of small, clear vesicles, and from three to 11 large dense core vesicles. In some cases the terminals were seen in continuity with more proximal processes of neurons in the RVL. These terminals formed synapses with a few perikarya and many dendrites, some of which also contained SPLI. In the material dually labeled for TH and SP, terminals with SPLI (n = 32) formed synaptic junctions primarily with TH-labeled dendrites (69%); the remainder were with TH-labeled perikarya (6%) or with unlabeled dendrites (25%). The axosomatic junctions were exclusively symmetric, whereas the majority of axodendritic junctions were primarily asymmetric on small dendrites (0.8-1.0 micron in diameter) or dendritic spines. In sections dually labeled for PNMT and SP, the terminals containing SPLI (n = 37) formed synaptic associations with PNMT-labeled perikarya (11%), PNMT-immunoreactive dendrites (59%), or with perikarya and dendrites lacking PNMT immunoreactivity (30%). The axosomatic junctions were all symmetric and most often associated with the spinous portion of the soma. The axodendritic junctions were primarily asymmetric and were found both on the spinous portion of the PNMT-labeled dendrites. In addition, both TH- and PNMT-labeled somata and dendrites received symmetric and asymmetric contacts from terminals lacking SPLI.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Ultrastructural characterization of substance P-like immunoreactive neurons in the rostral ventrolateral medulla in relation to neurons containing catecholamine-synthesizing enzymes. 245 38

In order to maintain a chronic supply of growth factor for medulla cells in vitro, chromaffin cells from rat, African green monkeys and man were co-cultured with C6 glioma cells, which secrete growth factors that sustain sympathetic neurons in vitro. The response of chromaffin cells to coculture was compared to treatment of medullary cells with nerve growth factor (NGF) alone. Dispersed chromaffin cell preparations were obtained by a trypsin-collagenase procedure, and subjected to differential plating on collagen-coated surfaces. With both human and monkey tissue, non-chromaffin cells did attach to the culture plates and an enriched chromaffin cell population could be replated. Rat adrenal medulla cells survived very poorly in vitro and were not enriched in this procedure. Cultured human and monkey chromaffin cells survived as epithelial cells (50%) and showed neuritic outgrowth on 55 to 66% of the cells after eight days when treated with nerve growth factor (NGF). These cells showed strong catecholamine histofluorescence, tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) immunoreactivity. In contrast, only ten percent of adult rat chromaffin cells survived in culture, although NGF treatment rescued an additional 20% of the cells and induced neuritic outgrowth after one week in vitro. C6 glioma cells were treated with mitomycin C bromodeoxyuridine to inhibit mitosis and were plated with the various medulla cells in a one to one ratio. Both human and monkey chromaffin cells expressed extensive and enhanced neuritic arborization within eight days of co-culture, (64-82% respectively) and exhibited intimate contact with the glioma cells as seen at the ultrastructural level. Importantly, survival of adult rat adrenal medulla cells was enhanced to 50% or more with 40% of the cells extending neurites when co-cultured with glioma cells for seven days. Chromaffin cells from all three species reacted for TH, DBH and PNMT in co-culture and were histo-fluorescent. The majority of these cells were also immunoreactive for serotonin and enkephalin, while only 37% of chromaffin cells indicated the presence of NPY. These data indicate that adrenal medulla can be maintained in vitro as the neuronal phenotype when co-cultured with growth factor producing cells and that this strategy may be useful for in vivo transplantation studies.
 ...
PMID:Rodent and primate adrenal medullary cells in vitro: phenotypic plasticity in response to coculture with C6 glioma cells or NGF. 256 44

Pharmacological and biochemical studies suggest that interactions between cholinergic and catecholaminergic and catecholaminergic neurons, particularly those of the C1 adrenergic cell group, in the rostral ventrolateral medulla (RVL) may be important in cardiovascular control. Ultrastructural localization of choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine, and its relation to neurons exhibiting immunoreactivity for catecholamine- (tyrosine hydroxylase; TH) or adrenaline (phenylethanolamine-N-methyltransferase; PNMT) -synthesizing enzymes were examined in the RVL using dual immunoautoradiographic and peroxidase anti-peroxidase (PAP) labeling methods. By light microscopy, the ChAT-immunoreactive neurons were located both dorsally (i.e. the nucleus ambiguus) and ventromedially to those labeled with TH or PNMT (TH/PNMT). A few ChAT-labeled processes were dispersed among TH/PNMT-containing neurons with the majority of overlap immediately ventral to the nucleus ambiguus. By electron microscopy, ChAT-immunoreactivity (ChAT-I) was detected in neuronal perikarya, dendrites, axons and axon terminals and in the vascular endothelial cells of certain blood vessels. The ChAT-labeled perikarya in the ventromedial RVL were medium-sized (15-20 microns), elongated, contained abundant cytoplasm and had had slightly indented nuclei. Synaptic junctions on ChAT-immunoreactive perikarya and dendrites were primarily symmetric with 64% (45 out of 70) of the presynaptic terminals unlabeled. The remaining terminals were immunoreactive for ChAT (30%) or TH/PNMT (6%). Terminals with ChAT-I were large (0.8-2.0 microns) and contained numerous small clear vesicles and 1-2 dense core vesicles. Seventy-seven percent (112 out of 145) of the ChAT-labeled terminals formed symmetric synapses with unlabeled perikarya and dendrites, whereas only 8% were with TH/PNMT-labeled perikarya and dendrites, and 15% were with ChAT-immunoreactive perikarya and dendrites. We conclude (1) that cholinergic neurons in the RVL principally terminate on and receive input from non-catecholaminergic neurons, and (2) that the reported sympathetic activation following application of cholinergic agents to the RVL may be mediated by cholinergic inhibition of local inhibitory interneurons. The observed synapses between ChAT and TH/PNMT-containing neurons suggests that cholinergic and adrenergic neurons additionally may exert a minor reciprocal control on each other and thus may modulate their response to the more abundant input from afferents containing other transmitters.
 ...
PMID:Ultrastructural localization of choline acetyltransferase in the rat rostral ventrolateral medulla: evidence for major synaptic relations with non-catecholaminergic neurons. 257 7

Expression and development of specific markers of the adrenergic phenotype were studied in central neurons grown in transplant system. Medulla oblongata from embryonic day 12.5 (E12.5) or E18 rat was grafted into the anterior chamber of the eye of adult rat hosts. After two months, grafts were examined for the presence of immunoreactivity (IR) and catalytic activity to the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28), a specific adrenergic marker. In addition, grafts were examined for immunoreactivity to neuropeptide Y (NPY) and tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. In E12.5 grafts, PNMT was expressed de novo, enzyme activity developed to levels similar to those in adult rat brainstem and PNMT-IR neurons were observed. TH-IR and NPY-IR neurons were also observed. In contrast, PNMT-IR was not observed in E18 grafts even though these already contained PNMT-IR neurons at the time of grafting. This was not due to poor growth of E18 grafts, in general, since TH-IR neurons were present and the protein content of the grafts was similar to that of E12.5 grafts. These studies suggest that adrenergic neurons survive well in oculo if they are transplanted prior to the age when neuroblasts have initially expressed the adrenergic phenotype, migrated to their final positions and elaborated processes. In addition, these studies establish a transplant system in which factors required for the development of central adrenergic neurons can be more easily studied than in situ.
 ...
PMID:Expression of phenylethanolamine N-methyltransferase (PNMT) and neuropeptide Y (NPY) in embryonic rat medulla oblongata grown in Oculo. 326 46

The involvement of adrenal hormones as regulatory factors in maintaining physiological levels of tyrosine hydroxylase (TH) was examined in mouse superior cervical ganglion. Following bilateral adrenalectomy, TH activity in the ganglion fell at a slow but steady rate, reaching 60-65% of the control levels after 2 weeks. Decentralization is known also to reduce TH activity in the ganglion. The effects of adrenalectomy and decentralization were therefore compared, and they were found to be additive, indicating different mechanisms in the two cases. The reduction of TH activity following adrenalectomy was not prevented by replacement with corticosterone (0.5 mg/kg, daily). However, replacement with epinephrine (4 mg/kg, daily) completely prevented the fall of TH activity in adrenalectomized animals. Isoproterenol, a beta-adrenergic receptor agonist, was as effective as epinephrine in preventing the reduction of TH activity following adrenalectomy. Furthermore, in intact animals, chronic administration of SKF 64139, an inhibitor of adrenal PNMT which depletes circulating epinephrine levels, also reduced ganglionic TH activity to the same level as that after adrenalectomy. These results indicate that epinephrine, but not corticosterone, is the adrenal factor required for physiological maintenance of normal levels of TH in the superior cervical ganglion.
 ...
PMID:Adrenal influence on tyrosine hydroxylase activity in superior cervical ganglion. 610 52


1 2 3 Next >>