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)

Dopa decarboxylase (DDC; aromatic-L-amino-acid decarboxylase; aromatic-L-amino-acid carboxylase, EC 4.1.1.28) was purified from rat liver and its partial sequence was determined. Synthetic oligonucleotides were used to construct and screen rat liver cDNA libraries, and three clones were isolated and sequenced. The 2 kilobases of DDC cDNA cloned consisted of a 5'-noncoding segment of 78 nucleotides, a coding region of 1440 nucleotides, and a 3'-noncoding region of 438 nucleotides. The encoded protein of 480 amino acid residues had a molecular weight of 54,000. A special feature of the primary structure of rat DDC was a repeating structure consisting of 29 amino acid residues. A sequence of 58 amino acid residues, including this repeating structure of rat DDC, was found to show homologies with those of rat tyrosine hydroxylase, human dopamine beta-hydroxylase, and bovine phenylethanolamine N-methyltransferase, other mammalian enzymes that synthesize catecholamines. These results indicate that catecholamine biosynthetic enzymes are structurally related and suggest that their homologous domains are important for catechol-protein interactions.
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PMID:Molecular cloning and sequencing of a cDNA of rat dopa decarboxylase: partial amino acid homologies with other enzymes synthesizing catecholamines. 281 83

The A1 noradrenergic cell group in the caudal ventrolateral medullary reticular formation of the rat sends efferent projections to a number of regions in the basal forebrain and hypothalamus, but the extent to which these projections represent collateral branches of individual axons is not known. Immunohistochemical labeling of medullary neurons containing the catecholamine biosynthetic enzymes tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase was used to reveal the anatomical location of A1 noradrenergic neurons within the ventrolateral medulla. Subsequently, the retrograde fluorescence double-labeling technique was employed to investigate the collateralization of ascending A1 efferent axons. The subcommissural bed nucleus of the stria terminalis (BST) was injected with rhodamine-fluorescent latex microspheres and the ipsilateral left paraventricular nucleus of the hypothalamus (PVN) was injected with Fast blue. Within the ventrolateral medulla, single- and double-labeled neurons were identified in a distribution corresponding to that demonstrated for A1 noradrenergic perikarya. The results indicate that some ascending axons from cells within the A1 region collateralize to effect a simultaneous innervation of the BST and PVN. The innervation of multiple efferent targets by single neurons within the A1 region may have important implications with respect to A1's postulated role in central cardiovascular regulation.
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PMID:Collateral axonal projections from the A1 noradrenergic cell group to the paraventricular nucleus and bed nucleus of the stria terminalis in the rat. 284 38

In this study, we sought to determine whether neurons of the chick embryo ciliary ganglia (CG), a parasympathetic cholinergic ganglia, can express catecholaminergic (CA) traits. To accomplish this, we used immunocytochemical techniques to examine the presence of the CA enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) in CGs removed from chick embryo at day 8 of development (E8). Few neurons containing TH but not PNMT were found in the E8 CG. To examine whether CG neurons express CA enzymes in vitro, CGs removed from E8 chick embryo were dissociated and kept in culture for 3 to 12 days. In 50% of the culture dishes, some neurons contain TH or PNMT after 5 days in vitro. In an equal proportion of culture plates, CG neurons did not express the enzymes. To determine whether the proportion of CG neurons expressing TH or PNMT is increased by tissue influences, ganglion cells were co-cultured with notochord. In 90% of the co-culture experiments, most neurons present in the culture dishes stained with TH or PNMT after 5 days in vitro. To test for the presence of aromatic L-amino acid decarboxylase (AADC), another CA enzyme, cultures of CGs and CGs plus notochord were incubated with levodopa and processed for the detection of CA histofluorescence. Dopamine histofluorescence was present in all neurons after 3 days in vitro irrespective of the presence of notochord, suggesting that the expressions of TH and PNMT and that of AADC are differentially regulated. This study, therefore, demonstrates that cholinergic neurons of the CG contain CA enzymes in vivo and in vitro and that the proportion of neurons expressing CA traits during development in vitro can be increased by environmental cues such as those released by the notochord.
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PMID:Cholinergic neurons of the chick ciliary ganglia express adrenergic traits in vivo and in vitro. 285 35

We examined serial 40 micron vibratome, immunoperoxidase-stained sections of the medulla with tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) antisera followed by Nissl staining to locate catecholaminergic neurons in cytoarchitectonic regions followed by a three-dimensional (3D) computer reconstruction of these cell groups to determine their spatial organization. Overlay drawings of low and high power photomicrographs showing cell bodies and nuclear boundaries were entered into a digital computer storage system. Every section in the series was plotted to yield an accurate representation of regional densities of cells and location of nuclei, as revealed by two-dimensional plots of individual sections as well as three-dimensional plots of groups of sections. Data files were scanned in a number of ways to obtain total cell counts of TH-, DBH-, and PNMT-immunoreactive cells within a designated area or cell counts of only one type of immunoreactive cell. This combination of data manipulation produced the following results: (1) A1 group is a homogeneous population of noradrenergic neurons at levels caudal to the obex, and at the obex it is mixed with adrenergic cells. The dimensions of the A1 cell group are 1.3 X 2.7 mm, extending from -2.5 to +0.2. Part of this cell group lies in the lateral reticular nucleus. (2) A2 group is not purely noradrenergic as previously suspected. It is a very mixed cell group containing mainly dopaminergic neurons in the area postrema (periventricular region) and the dorsal motor nucleus of the vagus, mainly noradrenergic neurons in the medial subnucleus of the nucleus of the tractus solitarius (nTS), mainly adrenergic neurons in the dorsal strip and dorsal subnucleus of the nucleus of the tractus solitarius, and a mixture of all three catecholaminergic neurons in the other subnuclei of the nTS. The dimensions of this group are 0.4 X 3 mm extending from -2.7 to +0.3. (3) C1 group is a homogeneous population of adrenaline cells extending from +1 to +2.5 with dimensions of 1.5 X 1.5 mm and consisting of scattered neurons some of which occupy the gigantocellular reticular nucleus. (4) C2 group is a homogeneous population of adrenaline neurons extending from +1 to +3 with dimensions of 2.5 X 3 mm. Accurate visual imaging and quantitation of the spatial organization of medullary catecholaminergic neurons within the classical anatomical framework of cytoarchitecture provides an enhanced comprehension of the organization of this region of the central nervous system.
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PMID:Rat medulla oblongata. IV. Topographical distribution of catecholaminergic neurons with quantitative three-dimensional computer reconstruction. 285 99

We found that the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) (EC 1.14.16.2), dopamine beta-hydroxylase (EC 1.14.17.1), and phenylethanolamine N-methyltransferase (EC 2.1.1.28) share similar protein domains in their primary structures and that they share common gene coding sequences. In a recent report we also demonstrated that antiserums directed against choline acetyltransferase (EC 2.3.1.6), glutamic acid decarboxylase (EC 4.1.1.15), and TH cause specific complement-mediated lysis of cholinergic, gamma-aminobutyric acid-ergic, and dopaminergic subpopulations of synaptosomes, respectively. This interaction of specific antibodies to the specific subpopulation of synaptosomal membrane, e.g., recognition of antibody to TH to only the dopaminergic subpopulation of synaptosomal membrane protein, indicates that the neurotransmitter enzyme and membrane protein of its own synaptosomes may also share common protein domains. Therefore, we postulate that the specific neurotransmitter biosynthetic enzyme and a certain membrane protein of the nerve endings may share similar gene coding sequences, and that expression of these proteins may determine the phenotype of the neuron.
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PMID:Genes for neurotransmitter synthesis, storage, and uptake. 286 77

The development of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) in the rat retina was investigated using the indirect immunofluorescence technique. Two types of TH-positive cells were found. The first appeared at postnatal day 2, in the vitreal half of the inner nuclear layer (INL). Single fibres from these neurones, bifurcating in and innervating layer 3 of the inner plexiform layer (IPL) were seen at day 4. This first type of TH-positive cell was most numerous at day 15, but thereafter disappeared before adulthood. At day 5, a more intensely staining TH-immunoreactive neurone became visible, occupying a more proximal part of the INL, and projecting multiple fibres to layer 1 of the IPL. In contrast, PNMT-positive cells, in the vitreal half of the INL and in the ganglion cell layer (GCL), sending single varicose axons to layer 3 of the IPL, were first apparent only at day 10, achieving a disposition similar to that of the adult by days 15-16 postnatal. Analysis of adjacent sections stained with antibodies to TH and PNMT revealed that neither type of TH-positive neurone also contained PNMT-like immunoreactivity. It is concluded that although both of the rate-limiting enzymes of the catecholamine synthetic pathway are present in the developing rat retina, they occur in 3 mutually exclusive populations of neurones.
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PMID:Differential ontogeny of three putative catecholamine cell types in the postnatal rat retina. 286 87

The appearance of phenylethanolamine N-methyltransferase (PNMT)- and tyrosine hydroxylase (TH)-like immunoreactivity (LI) in the foetal rat central nervous system has been investigated. Antibodies raised against PNMT and TH were used in an indirect immunofluorescence method. Attention was focussed on areas containing putative adrenaline-containing nerve cell bodies or fibres and, using an elution-restaining technique, it was possible to analyze whether neurones contained PNMT-LI, TH-LI, or both. PNMT-immunoreactive neurones could first be visualized on day 13 of gestation, in the ventrolateral and dorsal medulla oblongata, and probably corresponding to those of the C1 and C2 groups. The number of positive cell bodies and the intensity of their fluorescent staining in these areas were not dissimilar at this stage to the number and intensity observed at 1 day postnatal, the final age studied. At day 16, PNMT-positive cells were observed for the first time in midline areas of the rostral dorsal medulla oblongata-caudal pons, associated with the medial longitudinal fasciculus. These cells probably composed the C3 cell group. Many PNMT-immunoreactive fibres could be seen at day 13 of gestation, in the medulla, and coursing both in an ascending bundle around the mesencephalic flexure and in a descending bundle toward the spinal cord. The extent of the bundles increased with gestational age, such that dense meshworks of PNMT-immunoreactive varicose fibres were visible ventral to the aqueductus Sylvii, and the periventricular and lateral regions of the hypothalamus by days 18 to 19, and in the paraventricular nucleus, the septum, and the thoracic spinal cord by day 1 after birth. A sparser fibre plexus was observed in the amygdala at day 1 postnatal. In contrast to the explosive appearance of PNMT-immunoreactive cells at day 13 of gestation, the development of TH-LI within these same neurones was much more protracted. Only rarely were TH-LI and PNMT-LI colocalized at day 13, and even at birth TH-LI could not be visualized in 5% of PNMT-immunoreactive cells in the ventrolateral medulla oblongata, and in 50% of those in the dorsal vagal complex. A similar tardy appearance of TH-LI in PNMT-immunoreactive fibres was observed also. It should be emphasized that strongly TH-immunoreactive neurones were found already at gestational day 10.5 in the medulla oblongata, caudal to the PNMT-immunoreactive cells. It is concluded that the expression of enzymes involved in the synthesis of adrenaline is not unitarily controlled, and may be partly dependent on other than epigenetic factors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ontogeny of phenylethanolamine N-methyltransferase- and tyrosine hydroxylase-like immunoreactivity in presumptive adrenaline neurones of the foetal rat central nervous system. 286 76

We found that the catecholamine biosynthetic enzymes, tyrosine hydroxylase, dopamine B-hydroxylase and phenylethanolamine N-methyltransferase share similar protein domains in their primary structures, and therefore are coded for by a single gene or a family of genes. In a recent report, we also demonstrated that antisera directed against tyrosine hydroxylase, choline acetyltransferase and glutamate decarboxylase cause specific complement-mediated lysis of dopaminergic, cholinergic and GABA-ergic subpopulation of synaptosomes, respectively. This implies that the neurotransmitter biosynthetic enzyme and the specific nerve ending protein(s) also share similar protein domain(s). Therefore, we postulate that the specific neurotransmitter biosynthetic enzyme and a certain membrane protein of the nerve endings probably share similar gene coding sequences and that coordinate expression of these proteins may determine the phenotype of the neuron.
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PMID:Genes for neurotransmitter synthesis, storage and release. 286 55

We sought to characterize in detail neurons in rat retina that contain phenylethanolamine N-methyltransferase (PNMT), the epinephrine biosynthetic enzyme. Cell bodies and processes of PNMT-containing neurons in retina were identified by immunohistochemistry. The coexistence of other catecholamine biosynthetic enzymes in the same cells was also investigated. Biochemical, molecular biological and immunochemical methods were applied to determine whether retinal PNMT is similar to the adrenal enzyme, since regulation of PNMT in retina and adrenal appears to be different. The results show that there are two types of PNMT-containing cells: those containing PNMT exclusively and those containing PNMT with two other catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC), but not dopamine beta-hydroxylase (DBH). PNMT-only cell bodies are localized in the inner nuclear layer (INL) and the ganglion cell layer (GCL). Their processes are observed in outer and inner strata of the inner plexiform layer (IPL). Only a small fraction of PNMT neurons in INL also contain TH and AADC. These cells send their processes to the adjacent stratum of the IPL. Antibodies to bovine adrenal DBH, however, fail to localize DBH in any rat retinal cells. Immunochemical titration shows that PNMT from both retina and adrenal gland has the same immunoreactivity. Furthermore, a PNMT-cDNA probe hybridizes equally with PNMT-mRNA isolated from both the retina and the adrenal gland. These results indicate that PNMT is identical in these tissues.
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PMID:Phenylethanolamine N-methyltransferase-containing neurons in rat retina: immunohistochemistry, immunochemistry, and molecular biology. 287 Nov 39

Tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and phenylethanolamine N-methyltransferase, EC 2.1.1.28) are involved in catecholamine biosynthesis and are considered soluble proteins. However, they may actually be localized on the surface of the chromaffin granule. We have used the detergent digitonin to permeabilize the plasma membrane of cultured adrenal chromaffin cells to investigate the subcellular localization of TyrOHase and PMTase. A digitonin titration of the release of proteins and catecholamines revealed the existence of at least three subcellular compartments that are distinguished by their digitonin sensitivity: (i) soluble proteins, which were released upon treatment of the cells with low digitonin concentrations (5 microM), (ii) a "digitonin-sensitive" cytoplasmic protein pool, which required higher concentrations of digitonin for release (10 microM) and included TyrOHase and PMTase, and (iii) the chromaffin granule, which was insensitive to digitonin. Analysis of the rates of release of all of these proteins revealed that the rate of TyrOHase and PMTase release was slower at 10 microM than at 40 microM digitonin, while the rates of release of the other proteins were similar at both concentrations and varied in proportion to their respective sizes. Treatment with cytoskeletal disrupting agents had no effect on TyrOHase or PMTase efflux. These data suggest that TyrOHase and PMTase are in a detergent-labile association in the cell. This is consistent with the concept that TyrOHase and PMTase may be localized on the surface of the chromaffin granule.
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PMID:Restricted diffusion of tyrosine hydroxylase and phenylethanolamine N-methyltransferase from digitonin-permeabilized adrenal chromaffin cells. 287 56


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