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)

A cardiovascular-active pressor area of medullary reticular formation was defined by mapping changes in arterial blood pressure produced by microinjections of the neuroexcitatory amino acid, L-Glutamate (L-Glu). Sites where L-Glu provoked pressor responses larger than 10 mmHg were localized to a rostral longitudinal cell column of the nucleus reticularis rostroventrolateralis (n.RVL) extending 450 microns posteriorly to the facial nucleus. Spinal projections from the ventrolateral medulla were studied with a dual retrograde transport-immunocytochemical method. A striking correspondence was observed between the ventrolateral pressor area (VLPA) of n.RVL and rostrocaudal distribution of a circumscribed population of thoracic reticulospinal neurons containing tyrosine hydroxylase (TH)- or phenylethanolamine N-methyltransferase (PNMT)_immunoreactivity. Quantitative analysis revealed that 72% of the total number of retrogradely labeled neurons within the active area were immunocytochemically positive for TH; 28% of the reticulospinal projection cells were immunonegative. Deposits of L-Glu and dye through the same micropipettes verified a consistent correlation of vasopressor sites and the rostral subset of catecholaminergic neurons. Since comparable numbers of cell bodies in the VLPA contain TH and PNMT all are presumed to be adrenergic. At levels of n.RVL immediately adjacent to the VLPA commencing at a level 450 microns caudal to the facial nucleus, sites were unresponsive to Glu-stimulation or vasodepressor. At these levels, only non-adrenergic reticulospinal neurons project to cervical or thoracic spinal segments. We conclude that the VLPA is highly restricted to a narrow column of n.RVL < 0.5 mm in length and corresponds precisely with a population of predominantly adrenergic thoracic reticulospinal neurons that project exclusively to sympathoadrenal preganglionic motoneurons [cf 46]. These findings corroborate the idea that an adrenergic-spinal pathway may play a role in controlling sympathetic outflow.
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PMID:Adrenergic and non-adrenergic spinal projections of a cardiovascular-active pressor area of medulla oblongata: quantitative topographic analysis. 753 95

Visceral feedback circuits in lower brainstem were elucidated with retrograde tracers by mapping neurons that issue local projections to the general visceral afferent division of the nucleus tractus solitarii (NTS) and dorsomotor vagal nucleus (DMX) in adult male rats. In study 1, spinal and intramedullary afferents to the visceral-sensorimotor complex (NTS-X) were traced to contiguous populations of cell bodies arranged in cylindrical segmental organization. NTS-X afferents derive from curvilinear arrays of neurons that parallel the efferent radiations of the solitariotegmental tract. Newly discovered afferents arise from circumscribed cell groups in the dorsal reticular formation and periventricular zone. Another source was traced to a paraambigual cell column in the apex of the rostral ventrolateral reticular nucleus (n.RVL). In study 2, catecholaminergic afferents were initially defined with combined retrograde transport-immunocytochemical methods. Deposits of retrograde tracers into NTS-X transported to neurons containing tyrosine hydroxylase (TH) in the A1, C1, and C3 areas or phenylethanolamine N-methyltransferase (PNMT) in the C1 area of the n.RVL and C3 area. In study 3, it was revealed that NTS-X afferents arise, in part, as collaterals of thoracic reticulospinal neurons. Deposits of the retrograde fluorescent tracer Fluorogold into the upper thoracic cord and rhodamine-labeled microbeads into NTS-X transported to the same neurons within a subambigual locus in n.RVL and parts of nucleus raphe magnus. In study 4, dual retrograde tracer-immunocytochemical analysis demonstrated that catecholamines are synthesized by a subset of neurons in the n.RVL that issue collaterals to the NTS-X and thoracic cord. Double retrogradely labeled TH- or PNMT-immunoreactive cell bodies were restricted to the C1 area within a 450-microns column bordered rostrally by the facial nucleus and ventrally by the medullary subpial surface. We conclude that visceral reflex arcs are reciprocally organized. Targets of NTS projection are also sources of local NTS-X afferent innervation. Catecholaminergic and other local afferents from reticular formation, periventricular, and spinal gray may, via collaterals, simultaneously modulate visceral reflex excitability at the level of NTS and the outflow of autonomic and respiratory motoneurons.
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PMID:Medullary visceral reflex circuits: local afferents to nucleus tractus solitarii synthesize catecholamines and project to thoracic spinal cord. 753 75

The effects of insulin-like growth factor-I (IGF-I) on gene expression and the activities of the three enzymes specific for catecholamine biosynthesis, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), were determined in bovine adrenomedullary chromaffin cells primary cultured in serum-free medium. The mRNA level of TH was maximally elevated in the presence of IGF-I by 3.1 +/- 0.4-fold after 48 h, DBH by 5.1 +/- 0.3-fold in 24 h, and PNMT by 2.8 +/- 0.5-fold in 72 h. In addition, the activity of TH was increased by 77%, DBH by 70%, and PNMT by 23% in IGF-I-exposed cultures. In the absence of the growth factor, the mRNA levels of TH and DBH were decreased to 45 +/- 10% and 35 +/- 12% of the time-zero control within 48 h while PNMT mRNA was decreased to 82 +/- 5% only after 72 h. When the cells were cotreated with the protein tyrosine kinase inhibitor genistein, DBH induction by IGF-I was suppressed, confirming that the effect is mediated by tyrosine kinase. Cotreatment with the protein kinase A (PKA) inhibitor H89 caused complete reversal of the IGF-I-induced DBH increase and the effects of IGF-I treatment and PKA activation by forskolin were not additive, suggesting that PKA is involved in the signaling initiated by IGF-I in these cells.
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PMID:Induction of gene expression of the catecholamine-synthesizing enzymes by insulin-like growth factor-I. 759 82

We determined the effect of Ca++ influx on dopamine beta-hydroxylase (DBH) gene expression in primary cultured bovine chromaffin cells. The Ca++ ionophore A23187 (100nM) specifically reduced DBH mRNA to 15 +/- 10% of the untreated control while tyrosine hydroxylase was induced (142 +/- 15%) and phenylethanolamine N-methyltransferase was unchanged (107 +/- 11%). This effect on DBH was also observed with ionomycin, reversed by EGTA and unaffected by cycloheximide. Depolarization by potassium also resulted in DBH reduction which was reversed by the voltage dependent Ca++ channel blockers nifedipine and verapamil. DBH mRNA level reduced by A23187 could be re-induced by forskolin and DBH induced by forskolin could be reduced by the ionophore, suggesting that the cAMP and Ca++ pathways might act independently in regulating DBH gene expression.
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PMID:Reduction of dopamine beta-hydroxylase gene expression by calcium in bovine chromaffin cells. 759 16

As adrenal medullary chromaffin cells express imidazoline binding sites in the absence of alpha 2-adrenergic receptors, these cells provide an ideal system in which to determine whether imidazolines can influence catecholamine gene expression through nonadrenergic receptors. This study evaluates the ability of clonidine and related drugs to regulate expression of the gene for the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT) in the rat adrenal gland and in bovine adrenal chromaffin cell cultures. In vivo, PNMT and tyrosine hydroxylase (TH) mRNA levels increase in rat adrenal medulla after a single injection of clonidine. Clonidine also dose-dependently stimulates PNMT mRNA expression in vitro in primary cultures of bovine chromaffin cells, with a threshold dose of 0.1 microM. Other putative imidazoline receptor agonists, including cimetidine, rilmenidine, and imidazole-4-acetic acid, likewise enhance PNMT mRNA production showing relative potencies that correlate with their binding affinities at chromaffin cell I1-imidazoline binding sites. The effects of clonidine on PNMT mRNA appear to be distinct from and additive with those exerted by nicotine. Moreover, neither nicotinic antagonists nor calcium channel blockers, which attenuate nicotine's influence on PNMT mRNA production, diminish clonidine's effects on PNMT mRNA. Although 100 microM clonidine diminishes nicotine-stimulated release of epinephrine and norepinephrine in chromaffin cells, this effect appears unrelated to stimulation of imidazoline receptor subtypes. This is the first report to link imidazoline receptors to neurotransmitter gene expression.
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PMID:Regulation of phenylethanolamine N-methyltransferase gene expression by imidazoline receptors in adrenal chromaffin cells. 764 29

Several physiological studies have shown that the subcommissural organ (SCO) is influenced by catecholamines. This study provides immunohistochemical evidence for a noradrenergic input to the SCO of rats. A light plexus of tyrosine hydroxylase (TH)-and dopamine-beta-hydroxylase (D beta H)-positive axons present in the SCO of both Long-Evans and Sprague-Dawley rats. The innervation density was greatest in the hypendymal wing of the rostral aspect of the SCO and it declined both caudally in the hypendymal wing and medially in the hypendymal layer. Some TH- and D beta D beta H-immunoreactive fibers entered the lateral margin of the ependymal layer along the basal surface of ependymal cells; others coursed medially in the transverse plane to ramify along the base of the ependymal cells. These fibers are presumed to be noradrenergic because phenylethanolamine N-methyltransferase immunoreactivity was absent in adjacent sections through the SCO. Considering the potential role of the SCO region in sodium homeostasis, these data suggest that central noradrenergic input to the SCO may parallel peripheral catecholaminergic mechanisms that regulate sodium balance.
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PMID:Evidence for a noradrenergic projection to the subcommissural organ. 770 May 81

Tuberoinfundibular dopaminergic (TIDA) neurons, which represent the final common pathway in the inhibitory neuronal control of prolactin (PRL) secretion, are regulated by synaptic input from various transmitter systems. Because adrenergic receptors at hypothalamic sites were implicated in the central regulation of lactotrophs, we hypothesized that a synaptic communication might exist between adrenergic pathways ascending from the brain stem and the TIDA system. Polyclonal antisera directed towards phenylethanolamine N-methyltransferase (PNMT) and tyrosine hydroxylase (TH), biosynthetic enzymes of catecholamines, were used for the simultaneous immunocytochemical detection of adrenergic fibers and TIDA neurons, respectively, in Vibratome sections of the rat hypothalamus. By the light microscopic evaluation of double-immunostained sections, PNMT-immunoreactive (IR) axon varicosities were localized in juxtaposition to TH-IR cell bodies and dendrites in the arcuate nucleus (AN) which contains perikarya and dendrites of TIDA neurons. The ultrastructural analysis of contacts provided firm evidence for the occurrence of synaptic interactions between the adrenergic and TIDA neuronal systems. These morphological findings show that adrenergic neurons are involved in the afferent regulation of the TIDA system and indicate a putative pathway of central adrenergic effects upon PRL secretion.
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PMID:Adrenergic innervation of dopamine neurons in the hypothalamic arcuate nucleus of the rat. 771 98

Experiments were done in conscious rats to investigate the effect of intravenous infusion of hypertonic saline on the induction of the phosphoprotein Fos in brainstem catecholaminergic neurons. Fos induction, detected immunohistochemically, was used as a marker for neuronal activation. Infusions of 165 mM or 1.4 M NaCl solutions into the jugular vein resulted in Fos-like immunoreactivity in approximately the caudal two thirds of nucleus of the solitary tract (NTS), the caudal and rostral ventrolateral medulla (VLM), and in the lateral aspects of the parabrachial nucleus (PBN). Within caudal NTS a small number (7.9 +/- 1.8%) of Fos labelled neurons were found also to contain tyrosine hydroxylase (TH) or dopamine beta-hydroxylase (DBH) immunoreactivity. In rostral NTS no Fos labelled cells were found to contain phenylethanolamine N-methyltransferase (PNMT) immunoreactivity, although a few (8.5 +/- 2.3%) were immunoreactive to TH. Similarly, in VLM, most of the Fos labelled cells in caudal VLM (65.9 +/- 2.7%) contained either TH or DBH immunoreactivity, whereas in the rostral VLM, 32.2 +/- 4.6% of the Fos labelled cells were also immunoreactive to TH or DBH. However, no Fos cells were found in either the caudal or rostral VLM that were immunoreactive to PNMT. Little or no Fos-like immunoreactive neurons were detected in the brainstem after intravenous infusions of physiological (143 mM) or hypotonic (106 mM) NaCl solutions. These data suggest that noradrenergic neurons of the caudal NTS and VLM are components of central circuits that are involved in osmoregulation and cardiovascular function.
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PMID:Plasma hypernatremia induces c-fos activity in medullary catecholaminergic neurons. 777 94

The 'growth-associated protein', GAP-43 was originally considered to be a neuron-specific protein associated with plasticity. However, we have recently shown that GAP-43 is expressed by noradrenergic, but not by adrenergic chromaffin cells in the adult rat adrenal gland. In this study, we examine the expression of GAP-43 during embryonic and post-natal development of the adrenal gland using immunohistochemical techniques. In parallel, antibodies directed against two neuroendocrine markers, the catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were employed to permit identification of the developing chromaffin cell phenotypes. At embryonic day 15.5, GAP-43 was predominately localized in sympathoadrenergic precursor cells in the extra-adrenal blastema, and also in nerve fibers within the adrenal gland. At later embryonic stages, GAP-43 was expressed by nearly all intra-adrenal chromoblasts. Two subsets of chromoblasts can be distinguished even at early stages. A strong GAP-43-positive immunoreaction was observed in those chromoblasts organized in a few large compact clusters which weakly expressed TH and did not express PNMT. A generally weaker GAP-43 immunoreaction was observed in a second type of intra-adrenal chromoblasts which were organized in small isolated groups and characterized by a PNMT-positive, and strong TH-positive immunoreactivity. GAP-43 immunoreactivity was still associated with many PNMT-positive adrenergic chromoblasts at birth, but decreased to undetectable levels during the first post-natal week. By the second post-natal week, GAP-43 was restricted, as in the adult, to noradrenergic chromaffin cells which expressed TH, but not PNMT, in addition to nerve fibers and their associated glial cells in the gland. An immunoblot analysis confirmed a decrease in GAP-43 protein during the post-natal period. In agreement with these observations, a three-fold decrease in GAP-43 mRNA in the adrenal gland was measured between late embryogenesis and the second post-natal week. During development, the spatiotemporal expression of GAP-43 suggests a possible role in the migration and aggregation of chromaffin cell precursors into the medullary region of the adrenal gland.
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PMID:Expression of GAP-43 (neuromodulin) during the development of the rat adrenal gland. 784 14

The biosynthesis of catecholamines and indoleamines was investigated in the sea pansy Renilla koellikeri by radiochemical screening of tissue samples exposed in vivo to labelled amino acid precursors and analysed by high-performance liquid chromatography coupled with electrochemical detection. Incubation of sea pansy tissues in [3H]tyrosine resulted in substantial accumulation of radioactivity recovered in chromatograms coeluting with tyrosine and 4-hydroxy-3-methoxy mandelic acid and, to a lesser extent, with 3,4-dihydroxy-phenylalanine, dopamine, norepinephrine, epinephrine, normetanephrine and 3,4-dihydroxyphenyl acetic acid. The catecholamine synthesis inhibitor alpha-methyl-p-tyrosine effectively reduced several of these [3H]tyrosine by-products formed as well as endogenous stores of these amines. Incubations in [3H]tryptophan resulted in large amounts of radioactivity associated with liquid chromatographic peaks coeluting with tryptophan and 5-hydroxytryptophan and lesser amounts with 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine and 5-hydroxy-3-indole acetic acid. The indoleamine synthesis inhibitor p-chlorophenylalanine reduced the amounts of products formed and depleted stores of the endogenous indoleamines. Enzyme activities which appear to involve tyrosine hydroxylase (EC 1. 12. 16. 2), tryptophan hydroxylase (EC 1. 14. 16. 4) and phenylethanolamine N-methyltransferase (EC 2. 1. 1. 28) were also detected in rachidial tissues by HPLC analysis of reaction products (hydroxylases) and by a radioenzymatic assay (methyltransferase). The sea pansy being a representative of the earliest invertebrates possessing a nervous system, these results support the hypothesis that vertebrate-like enzymatic pathways for the biosynthesis and degradation of monoamine neurotransmitters were conserved throughout evolution.
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PMID:Evidence for biosynthesis and catabolism of monoamines in the sea pansy Renilla koellikeri (Cnidaria). 784 75


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