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)

In fasting, declining circulating thyroid hormone levels coincide with suppressed thyrotropin-releasing hormone (TRH) mRNA and peptide levels and elevated NPY release and binding in the parvicellular paraventricular nucleus (PVN). It is suggested that NPY, in parallel with triggering feeding behavior, interrupts normal thyroid feedback in food deprivation. To gain further insights into the involvement of NPY in the regulation of TRH cells, this study sought to elucidate the source of the NPY innervation of TRH neurons. The median forebrain bundle (MFB) that carries the ascending NPY fibers from the brain stem catecholaminergic nuclei was unilaterally transected. Animals were sacrificed 2 and 5 days after surgery and double immunocytochemistry for NPY and TRH or tyrosine hydroxylase (TH) and TRH was performed on sections from the PVN. Two days after the surgery, light microscopic examination revealed no changes in the numbers of NPY boutons making putative contacts with TRH cell bodies and proximal dendrites. On the other hand, under the electron microscope, NPY- and TH-immunoreactive fibers containing autophagous cytolysosomes, an early sign of catecholaminergic fiber degeneration, were found to establish asymmetric synapses on distal dendrites and dendritic spines of TRH-immunoreactive cells. However, the same electron microscopic analysis did not reveal any degenerating NPY-immunolabeled fibers in synaptic contact with TRH cell bodies and proximal dendrites. Five days after the surgery, when NPY and TH immunoreactivities were no longer detected in the ipsilateral MFB, no decrease in the numbers of NPY and TH boutons on TRH cell bodies and proximal dendrites could be detected, when compared to the contralateral side. Electron microscopy revealed fibers with Wallerian degeneration establishing asymmetric synapses exclusively on the distal dendrites and spines of TRH neurons. In conclusion, this study demonstrated that the NPY and catecholaminergic input on PVN TRH cells are of mixed origin. The cell bodies and proximal dendrites of TRH neurons receive a robust, putative inhibitory NPY input from the hypothalamus. The distal dendrites and dendritic spines of the TRH cells also receive a putative stimulatory NPY input from the brain stem catecholaminergic neurons. It is suggested that because of its proximal location and abundance, NPY of hypothalamic origin exerts a tonic inhibition on PVN TRH cells that interrupts negative thyroid feedback during food deprivation. Furthermore, it is likely that a general inhibition and not stimulation of parvicellular PVN activity may underlie the triggering of feeding behavior by hypothalamic NPY.
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PMID:Segregation of the intra- and extrahypothalamic neuropeptide Y and catecholaminergic inputs on paraventricular neurons, including those producing thyrotropin-releasing hormone. 980 1

Although stress is a major contributory factor in the development of depression, the relationship between stress and depression is still unclear. In this study, we evaluated basal mRNA levels of several genes involved in neurotransmitter biosynthesis and the effect of stress in Flinder's Sensitive Line (FSL), a genetic rat model of depression. In adrenals, basal levels of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT) and GTP cyclohydrolase I (GTPCH) mRNAs were markedly elevated in FSL rats compared to the control strain. As opposed to control strain, immobilization stress (IMO) to FSL rats, did not further raise DBH, PNMT or GTPCH mRNAs and had relatively mild effect on TH. In contrast to enzymes involved in catecholamine biosynthesis, basal NPY and its response to IMO were unchanged in FSL rats. In the brain, the two major dopaminergic nuclei displayed differences. In substantia nigra, TH mRNA levels were similar in both strains, and elevated by IMO only in FSL rats. In ventral tegmental area in FSL rats, TH mRNA was 2-fold higher than in the control strain and not further elevated by IMO. These high basal mRNA levels and abnormal response to stress in several catecholaminergic cell types in FSL rats may be related to the manifestations of depression.
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PMID:Altered gene expression for catecholamine biosynthetic enzymes and stress response in rat genetic model of depression. 983 81

Neurotransmitters are known to play an important role in the development of the nervous system. We recently generated transgenic mice that ectopically express tyrosine hydroxylase (TH) and thereby produce dopamine (DA) de novo in pinealocytes of the pineal gland (PG). The transgenic PG also exhibited a dramatic decrease in TH-immunoreactive (IR) fibers putatively arising from the superior cervical ganglion (SCG) (Cho et al. [1996] Proc Natl Acad Sci USA 93:2862-2866). In the current study, however, we found that there was no reduction in the number of fibers immunostained for neurofilament protein or PGP9.5, markers known to be heavily localized in fibers, despite the reduction of TH fiber density. Therefore, we investigated whether the decreased TH-IR fiber density is the consequence of reduced sympathetic innervation, or a decrease in TH expression within innervating fibers. Immunohistochemical analysis comparing control and transgenic PG demonstrated no apparent differences in numbers of NPY- and aromatic-L-amino acid decarboxylase (AADC)-IR fibers, indicating that TH expression is decreased in a normal number of innervating fibers. Furthermore, presynaptic neurons in the transgenic SCG showed abnormal and heterogeneous TH immunoreactivity and reduced TH and norepinephrine transporter (NET) mRNA levels. These results show that ectopic DA production in the PG lowers TH and NET gene expression in the SCG without altering sympathetic innervation to the PG and suggest that the alteration of target neurotransmitter phenotype may influence gene expression of phenotype-specific proteins in projecting neurons.
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PMID:Altered presynaptic gene expression in transgenic mice producing dopamine in the pineal gland. 1050 12

Single and double-label immunofluorescence methods were used to determine the distribution and patterns of colocalisation of various neuropeptides and nitric oxide synthase (NOS) with the catecholamine synthesising enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbetaH) in nerve fibres within specimens of adult human vas deferens obtained at vasectomy (age range 28 to 83 y). Cholinergic nerve fibres were immunolabelled with an antiserum to vesicular acetylcholine transporter (VAChT). Using the general nerve marker protein gene product 9.5 (PGP) the density of intramural nerve fibres was found to be similar irrespective of age. Many of these axons, especially in the outer 2 muscle layers were TH and DbetaH-immunoreactive (IR) and were thus confirmed as noradrenergic. Fewer such axons were seen in the inner longitudinal muscle layer. All the noradrenergic nerve fibres also displayed NPY-immunoreactivity with minor populations containing galanin (GAL) or somatostatin (SOM). Nerve fibres lacking TH and DbetaH-IR were immunoreactive for VAChT and were sparsely distributed throughout the 2 outer muscle layers but more numerous in the inner muscle layer. Nerves lacking TH and DbetaH were immunoreactive for NPY and some also contained NOS, VIP or CGRP. These results have been compared with those obtained previously from specimens of human neonatal and infant vas deferens where, in contrast to the present results, NOS and VIP were shown to be colocalised with TH in many of the intramuscular nerve fibres. It thus appears that NOS and VIP cease their coexistence with TH in intramuscular nerve fibres of the human vas deferens between the pre- and postpubertal states. In addition to the intramuscular nerve fibres a VAChT-IR subepithelial nerve plexus occurs in the vas deferens and may control the secretory activity of the lining epithelium. Most of these subepithelial nerve fibres were immunoreactive for NPY and many also contained VIP while minor populations were immunoreactive for NOS, GAL, SOM or SP although fibres containing CGRP were not observed. The neuropeptide content of the subepithelial nerve plexus was similar to that observed in the infant, except for an increased density of VIP-IR nerves, which may reflect greater activity of the lining epithelial cells in the adult vas deferens.
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PMID:Colocalisation of neuropeptides, nitric oxide synthase and immunomarkers for catecholamines in nerve fibres of the adult human vas deferens. 1069 95

In order to better understand the regulation of blood flow to tooth-related structures, the patterns of VIP- and NPY-ergic innervations in the rat were examined. Nerve fibers showing NPY-like immunoreactivity (NPY-LI) frequently occurred in the walls of the large main arteries, as well as in association with the arterioles, to a high degree co-existing with tyrosine hydroxylase (TH), whereas VIP-LI was mainly restricted to the walls of the large arteries. After sympathectomy, no NPY/TH-LI nerve fibers were seen in blood vessel walls. However, a NPY-immunoreactive nerve population remained in the walls of the large arteries, NPY- and VIP-LI co-existing in this nerve population. Both immunoreactions were intense. The present study suggests that a NPY/sympathetic innervation as well as a VIP innervation (large arteries) are likely to have substantial roles in the balance and maintenance of vasoregulation in tooth-related structures and that a NPY/VIP innervation becomes of particular importance when the NPY/sympathetic innervation is destroyed.
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PMID:NPY/sympathetic and NPY/VIP innervation of the blood vessels supplying rat tooth-related structures: effects of sympathectomy. 1065 95

We have identified a population of progenitor cells in embryonic dorsal root ganglia (DRG) of the mouse. These cells can be induced into proliferating and differentiating into neurons that display multiple characteristics of the sympathetic lineage by a brief exposure to a defined medium. The sympathetic neuronal characteristics include immunoreactivity for the transcription factors MASH-1 and Phox2a and for the neurotransmitter markers tyrosine hydroxylase, choline acetyltransferase, and NPY. The progenitor cells are detected in DRG from embryonic day 11.5 (E11.5) to E15. An identical time course is observed in primary cultures of neural crest, suggesting that the competency of these cells is intrinsically regulated. We also present evidence that the environment of the sensory ganglion, unlike that of a sympathetic ganglion, prevents these cells from differentiating into neurons.
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PMID:Progenitor cells with the capacity to differentiate into sympathetic-like neurons are transiently detected in mammalian embryonic dorsal root ganglia. 1075 64

The coeliac ganglion of guinea pigs displays a unique topographical arrangement of neurochemically and functionally distinct populations of sympathetic neurons. The authors used multiple-labeling immunohistochemistry to investigate the neurochemical differentiation of these neurons during embryonic and fetal development. Sympathoadrenal precursors, located on either side of the abdominal aorta, were intensely immunoreactive for tyrosine hydroxylase (TH-IR), neurofilament, and the human natural killer 1 antibody at midembryonic stages (Carnegie stages 16-19). During late embryonic stages (stages 20-23), a single bilobed ganglion had formed. At this time, neuropeptide Y immunoreactivity (NPY-IR) was widely expressed in sympathetic neurons (with moderate TH-IR) and chromaffin cells (with intense TH-IR). The onset of somatostatin (Som-IR) expression followed that of NPY-IR and was restricted to sympathetic neurons. However, at late embryonic stages, most TH-IR neurons with Som-IR also expressed NPY-IR (a combination of peptides not found in the mature coeliac ganglion). Between late embryonic stages and the end of the early fetal period, there was a significant increase in the proportion of neurons in lateral regions that had both NPY-IR and TH-IR. At the same time, there was an increase in the proportion of neurons in medial regions that had both Som-IR and TH-IR. Neurons expressing both Som-IR and TH-IR were rarely observed in lateral regions of the coeliac ganglion. Thus, a clear topography within the coeliac ganglion is established during late embryonic and early fetal stages of development and reflects that found in the mature animal by the end of the early fetal period.
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PMID:Neurochemical differentiation of functionally distinct populations of autonomic neurons. 1111 29

The distribution and ascending projections to the hypothalamic paraventricular nucleus of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive perikaria were studied in adult pigeons using a combination of retrograde transport of Fluorogold injected into the paraventricular nucleus, and double immunohistochemical procedures for PNMT, tyrosine hydroxylase and neuropeptide Y. PNMT-immunoreactive cell bodies were found in the subtrigeminal reticular nucleus of the ventrolateral medulla and in the nucleus of the solitary tract, mainly in the subnuclei: medialis superficialis, pars posterior, and medialis ventralis, pars posterior. PNMT-immunoreactive perikaria were also tyrosine hydroxylase immunoreactive, and are located within the rostral tyrosine hydroxylase immunoreactive cell groups of these areas. No perikaria double-labeled for neuropeptide Y and PNMT were found. Retrograde labeled cell bodies were observed in the subtrigeminal reticular nucleus and in the nucleus of the solitary tract. PNMT-immunoreactive retrogradely labeled cells were mainly observed in the subtrigeminal reticular nucleus. These data suggest the presence in the pigeon of medullary adrenergic cell groups partially comparable to mammalian C1 and C2 groups. Comparison of these results with data previously obtained in amphibians and reptiles suggests that the presence of a hypothalamically-projecting C1-like group might be a plesiomorphic medullary attribute in amniotes, whereas the variable presence of C2 and C3-like groups, as well as the content of NPY in the putative adrenergic perikaria, seem to be species-specific.
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PMID:Phenylethanolamine N-methyltransferase-immunoreactive neurons in the medulla oblongata of the pigeon (Columba livia) projecting to the hypothalamic paraventricular nucleus. 1115 97

The effects of five neuropeptides (CGRP, SOM, SP, NPY, VIP), L-NAME (nitric oxide synthase inhibitor), and adrenaline on the contractile tone of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus, were investigated. None of the neuropeptides, which had previously been found to be present in the aortic anastomosis, had any direct effect on the tension developed by ring preparations. L-NAME itself significantly increased the basal tone of the vascular ring preparations, suggesting a tonic release of nitric oxide in the preparation. Adrenaline produced concentration-dependent vasoconstrictions that were counteracted by profound reflex vasodilatations that were susceptible to blockade by L-NAME. Immunohistochemistry revealed the presence of nitric oxide synthase and tyrosine hydroxylase-containing (indicating the presence of a adrenergic innervation) nerve fibres in the adventitia and adventitio-medial border of the aortic anastomosis. These data demonstrate opposing actions of adrenaline and nitric oxide on the vascular smooth muscle in the anastomosis of the C. porosus. The morphology of the anastomosis, with the extremely thick muscular vessel wall, suggests a sphincter-like function for this vessel that could be controlled mainly by adrenergic and nitrergic mechanisms.
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PMID:Nitric oxide, a potent vasodilator of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus. 1131 25

Immunoreactivities (IR) for catecholamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DbetaH), phenylethanolamine N-methyl transferase (PNMT), serotonin-synthesizing enzyme tryptophan hydroxylase, and neuropeptide Y were investigated in the intrinsic cardiac nervous system of 27-40-day-old rats using fluorescent immunohistochemistry. Individual neurons were identified by the general neuronal marker protein gene product 9.5. The presence of DbetaH and PNMT in the atrial specimens was verified using reverse transcriptase-polymerase chain reaction. Two types of catecholamine-handling intrinsic ganglion neurons were observed: small intensely fluorescent (SIF) cells and large-diameter neurons. SIF cells exhibited TH- and tryptophan hydroxylase-IR, but they were not positive for DbetaH. In contrast, large-diameter intrinsic TH-positive neurons, showing in majority also NPY-IR, displayed also DbetaH- and PNMT-IR, thus indicating the capacity for the synthesis of norepinephrine and epinephrine, respectively. In conclusion, the SIF cells are most probably dopaminergic and serotonergic neurons, whereas large-diameter intrinsic cells seem to represent a subpopulation of norepinephrine- and/or epinephrine-secreting neurons.
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PMID:Catecholaminergic neurons in the rat intrinsic cardiac nervous system. 1267 49


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