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)

Neuropeptide Y receptors in the medulla oblongata participate in central cardiovascular control. The neuropeptide Y1 receptor subtype gene and amino acid sequence have been identified by molecular cloning studies. In this study, a C-terminal peptide representing amino acids 355-382 of the neuropeptide Y1 receptor was synthesized and cross-linked to thyroglobulin to produce an antibody against a partial sequence of the neuropeptide Y1 receptor, used to localize neuropeptide Y1 receptor-like immunoreactivity in the catecholaminergic neurons of the medulla oblongata. The double colour immunofluorescence technique with a polyclonal antibody against the neuropeptide Y1 receptor and a monoclonal antibody against tyrosine hydroxylase revealed that in the rat medulla oblongata, a weak (the C3 cell group) to moderately intense (the A1, A2, C1 and C2 cell groups), diffuse cytoplasmic neuropeptide Y1 receptor-like immunoreactivity was distributed primarily in the noradrenergic and adrenergic cell bodies and occasionally seen in the noradrenergic and adrenergic cell processes. Almost all tyrosine hydroxylase-like immunoreactive cell bodies in the A1, A2, C1, C2 and C3 cell groups showed neuropeptide Y1 receptor-like immunoreactivity. The neuropeptide Y1 receptor-like immunoreactivity in the A2 cell group was somewhat stronger. The present findings show localization of specific neuropeptide Y1 receptor-like immunoreactivity in the vast majority of the noradrenergic and adrenergic cell bodies of the A1, A2, C1, C2 and C3 cell groups, which are putative cardiovascular regions. The results support the view that neuropeptide Y1 receptors in the medulla oblongata are involved in central cardiovascular control and may coexist with another important receptor, the alpha 2A-adrenoceptor, also involved in central, cardiovascular regulation, since the alpha 2A-adrenoceptor-like immunoreactivity has been shown to exist in almost all noradrenergic and adrenergic cell bodies in the brainstem. In conclusion, centrally administered neuropeptide Y may act in part via neuropeptide Y1 receptors located on the soma and dendrites of noradrenergic and adrenergic neurons, where it may interact with alpha 2-adrenoceptors at least in the noradrenergic A2 neurons. This noradrenaline system may be involved in at least part of the vasodepressor actions of neuropeptide Y, noradrenaline and adrenaline in the nucleus tractus solitarii in view of the present findings.
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PMID:Localization of neuropeptide Y Y1 receptor-like immunoreactivity in catecholaminergic neurons of the rat medulla oblongata. 878 67

The postnatal development of intraadrenal ganglion neurons was studied in rat by using indirect immunohistochemistry and in situ hybridization. The large neuropeptide tyrosine (NPY)-expressing ganglion neurons (type I ganglion neurons) matured postnatally, with marked increases in acetylcholinesterase (AChE)-, neurofilament 10 (NF10)-, and tyrosine hydroxylase (TH)-like immunoreactivities (LIs) paralleled by increasing levels of mRNAs encoding NPY, low-affinity neurotrophin receptor (LANR), and tropomyosin kinase receptor (trk). The smaller vasoactive intestinal polypeptide (VIP)-immunoreactive (IR) ganglion neurons (type II ganglion neurons) expressed increasing levels of VIP mRNA postnatally and also contained immunoreactive nitric oxide synthase (NOS) and its mRNA. These type II ganglion neurons appeared to be relatively mature already at postnatal day (P2) and did not express detectable levels of LANR or trk mRNAs. The cell size of both the type I and type II ganglion neurons increased about 2.5-fold postnatally. The type I ganglion neurons formed more densely packed clusters with increasing age, whereas the type II ganglion neurons were spread out in small groups or individually, mainly in the peripheral parts of the medulla, and appeared to fulfill their migration into the medulla and/or to the inner regions of the cortex early postnatally, possibly after establishing contact with their cortical targets. We suggest that the type I ganglion neurons represent sympathetic ganglion neurons of the same origin as the chromaffin cells and that they mature mainly postnatally. The development of the type II (VIP/NOS) ganglion neurons takes place earlier; however, their phenotype remains more uncertain.
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PMID:Phenotype of intraadrenal ganglion neurons during postnatal development in rat. 884 13

Aspartate-like immunoreactivity was visualized in the neostriatum of rats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limpet hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)methamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxy-dopamine lesioned rats after multiple injections of the D1-dopamine receptor agonist SKF 38393. In these rats strongly fluorescent processes as well as extensive terminal varicose fibre networks were observed. This increase could partly be blocked by the D1-dopamine receptor antagonist SCH 23390. Using a modified technique the aspartate-positive cell bodies and processes were observed even when the antiserum was diluted 1:80,000. Positive cell bodies and fibres were also seen on the ipsilateral side outside the neostriatum, for example in the islet of Calleja and in the piriform cortex. The aspartate-positive cells were negative for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D1-receptor subtype. A proportion of the aspartate-positive neurons (20%) contained neuropeptide tyrosine-like immunoreactivity. On adjacent sections there was a marked up-regulation of preprodynorphin-like immunoreactivity. The up-regulation of dynorphin and aspartate was only observed when there was an almost complete denervation of the neostriatum as visualized with antiserum to tyrosine hydroxylase, a marker for dopamine fibres. The present results raise the possibility that aspartate may act as a neurotransmitter released from interneurons in the neostriatum.
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PMID:Evidence for aspartate-immunoreactive neurons in the neostriatum of the rat: modulation by the mesencephalic dopamine pathway via D1-subtype of receptor. 884 77

Neuropeptide Y (NPY)-containing neural projections to the rat pituitary gland were studied by combining NPY immunohistochemistry with retrograde tracing with Fluorogold as well as central and peripheral denervations. Numerous pituitary-projecting, i.e. Fluorogold-labelled, neurons in the superior cervical ganglion, as well as in the hypothalamic magnocellular nuclei were NPY-immunoreactive (NPY-IR). In contrast, no other hypothalamic NPY-IR neurons, e.g. in the arcuate nucleus or the preoptic area, were observed to be projecting into the pituitary. Within the posterior lobe of the pituitary gland two morphologically distinct NPY-IR fiber populations were discovered, namely thinner parenchymal terminals, distinct from the neurosecretory terminals, and thicker, perivascular fibers. Neurosecretory nerve terminals, in contrast, were devoid of NPY-IR, being consistent with the previous reports on their sensitivity to osmotic stimulation. On the other hand, the anterior and intermediate lobes contained no NPY-IR fibers. Bilateral extirpation of the superior cervical ganglion resulted in disappearance of the perivascular NPY-IR fibers leaving the parenchymal NPY-IR fibers unaffected, while transection of the pituitary stalk abolished all of the parenchymal NPY-IR neurons, leaving the perivascular fibers unaffected. These findings together with the observed colocalization of tyrosine hydroxylase and NPY in the posterior lobe perivascular fibers indicated that they are sympathetic nerve endings. The thin parenchymal terminals, instead, are suggested to stem from central sources other than hypothalamus. Our findings indicate that the pituitary gland receives NPY-containing innervation from at least three distinct sources, and NPY may thus affect pituitary functions in various ways, such as blood flow and vasopressin release.
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PMID:Pituitary gland receives both central and peripheral neuropeptide Y innervation. 897 22

The innervation of the thymus was studied in SCID mice: There was a relatively more dense innervation pattern in SCID mice as compared to normal BALB/c mice (from which SCID mice are derived), including nerve fibres immunoreactive for protein gene product 9.5 (PGP 9.5), tyrosine hydroxylase (TH), neuropeptide tyrosine (NPY) and vasoactive intestinal peptide (VIP), although there was no reactivity to substance P (SP) or leucine enkephalin (ENK). Only a few acetylcholinesterase (AChE)-positive nerve fibres were observed in the SCID thymus. Ten weeks after the transfer of bone marrow from normal BALB/c mice into SCID mice no immunoreactivity to the above markers was found, nor was there any AChE reaction, although histologically the thymus appeared normal and dot-blot assays demonstrated the presence of immunoglobulin indicating a return to normal bone marrow function in SCID mice. Both innervation and morphology were restored 6 months after bone marrow transfer. In conclusion, the thymus of SCID mice lacking thymocytes has visible neurotransmitter levels in the nerves, but after thymocyte repopulation by bone marrow transplantation the transmitters are generally not demonstrable. This indicates that the innervation may be more important for the establishment of the microenvironment rather than the maintenance of thymocyte differentiation.
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PMID:Innervation of the thymus in normal and bone marrow reconstituted severe combined immunodeficient (SCID) mice. 914 33

With the use of retrograde tracing techniques, selective spinal nerve transections, and immunohistochemistry to label noradrenergic and peptidergic pathways, this study has for the first time defined in detail the autonomic innervation to the rat seminal vesicles. The majority of this innervation originates from the bilateral major pelvic ganglia, whereas very few neurons are located in the accessory, inferior mesenteric, or paravertebral chain ganglia. Neuropeptide Y was the most abundant marker, followed by tyrosine hydroxylase (an enzyme involved in noradrenaline synthesis), and then vasoactive intestinal peptide. Sympathetic axons with tyrosine hydroxylase and neuropeptide Y supplied vascular and nonvascular smooth muscle whereas parasympathetic, cholinergic neuropeptide Y terminals were associated with the glandular epithelium. In contrast, vasoactive intestinal peptide was found only in cholinergic neurons, which may have either parasympathetic or sympathetic spinal connections. The latter were far more prevalent, demonstrating a substantial sympathetic cholinergic innervation to the seminal vesicles. Vasoactive intestinal peptide axons were associated with the glandular epithelia, as well as vascular and nonvascular smooth muscle. Axons associated with the secretory epithelia may regulate secretion or perhaps provide trophic support. Finally, acute damage to preganglionic sacral and lumbar nerves caused a transient increase in glandular weight.
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PMID:Location, immunohistochemical features, and spinal connections of autonomic neurons innervating the rat seminal vesicles. 936 84

It is well established that sensory perception becomes impaired with advancing age and that, in parallel, dystrophy and degeneration of axons occur in sensory pathways. In this study, the impact of aging was examined in the mystacial pad, which receives a large variety of sensory nerve endings organized in a highly predictable pattern. Mystacial pad specimens from aged (30 months old) and young adult (2-3 months old) female Sprague-Dawley rats were processed, in parallel, for immunohistochemical analyses with antibodies against human neuronal cytoplasmic protein (protein gene product 9.5), transmitter enzymes, and several neuropeptides. Several changes in cutaneous innervation including both degenerative and regenerative processes were evident in the aged rat: (1) the Merkel endings and lanceolate endings that emanate from large-caliber afferents in the whisker follicles were reduced and showed signs of degeneration. Furthermore, a reduction of piloneural complexes at the intervibrissal hairs were evident, but only in aged rats that showed more severe behavioral sensorimotor disturbances. In contrast, Ruffini endings as well as mechanoreceptors emanating from medium-caliber axons, i.e., transverse lanceolate and reticular endings, appeared normal. (2) A reduction was evident among two sets of unmyelinated epidermal endings; however, the epidermal innervation affiliated with the intervibrissal hairs appeared normal in the aged rat. (3) A loss of sympathetic neuropeptide tyrosine (NPY) or tyrosine hydroxylase-immunoreactive (IR) and somatosensory Calcitonin gene-related peptide (CGRP)-IR perivascular axons was paralleled by an increase in presumed parasympathetic NPY/CGRP-IR axons. (4) Two "novel" networks of fine-caliber axons were observed in the outer and inner root sheaths of the whisker follicles in the aged rat. (5) NPY was present in a population of small-caliber, somatosensory CGRP-IR axons in the aged rat. This may represent a de novo synthesis, since, normally, NPY-like immunoreactivity is not observed in this set of axons. Our results suggest that the sensory impairments occurring with advancing age are part of a peripheral process instigated by changes in nerve-target interactions and/or incapacitation of the neuronal machinery to sustain the axonal integrity.
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PMID:Alterations in mystacial pad innervation in the aged rat. 941 77

By the indirect immunofluorescence method, the distribution of nitric oxide synthase (NOS)-like immunoreactivity (LI) and its possible colocalization with neuropeptide immunoreactivities, with two enzymes for the catecholamine synthesis pathway, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), as well as the enzyme for the acetylcholine synthesis pathway, choline acetyltransferase (ChAT) were studied in the anterior pelvic ganglion (APG), the inferior mesenteric ganglion (IMG) and the hypogastric nerve in the male guinea pig. The analyses were performed on tissues from intact animals, as well as after compression/ligation or cut of the hypogastric nerve. In some cases the colonic nerves were also cut. Analysis of the APG showed two main neuronal cell populations, one group containing NOS localized in the caudal part of the APG and one TH-positive group lacking NOS in its cranial part. The majority of the NOS-positive neurons contained ChAT-LI. Some NOS-positive cells did not contain detectable ChAT, but all ChAT-positive cells contained NOS. NOS neurons often contained peptides, including vasoactive intestinal peptide (VIP), neuropeptide tyrosine (NPY), somatostatin (SOM) and/or calcitonin gene-related peptide (CGRP). Some NOS cells expressed DBH, but never TH. The second cell group, characterized by absence of NOS, contained TH, mostly DBH and NPY and occasionally SOM and CGRP. Some TH-positive neurons lacked DBH. In the IMG, the NOS-LI was principally in nerve fibers, which were of two types, one consisting of strongly immunoreactive, coarse, varicose fibers with a patchy distribution, the other one forming fine, varicose, weakly immunoreactive fibers with a more general distribution. In the coarse networks, NOS-LI coexisted with VIP- and DYN-LI and the fibers surrounded mainly the SOM-containing noradrenergic principal ganglion cells. A network of ChAT-positive, often NOS-containing nerve fibers, surrounded the principal neurons. Occasional neuronal cell bodies in the IMG contained both NOS- and ChAT-LI. Accumulation of NOS was observed, both caudal and cranial, to a crush of the hypogastric nerve. VIP accumulated mainly on the caudal side and often coexisted with NOS. NPY accumulated on both sides of the crush, but mainly on the cranial side, and ENK was exclusively on the cranial side. Neither peptide coexisted with NOS. Both substance P (SP) and CGRP showed the strongest accumulation on the cranial side, possibly partly colocalized with NOS. It is concluded that the APG in the male guinea-pig consists of two major complementary neuron populations, the cholinergic neurons always containing NOS and the noradrenergic neurons containing TH and DBH. Some NOS neurons lacked ChAT and could represent truly non-adrenergic, non-cholinergic neurons. In addition, there may be a small dopaminergic neuron population, that is containing TH but lacking DBH. The cholinergic NOS neurons contain varying combinations of peptides. The noradrenergic population often contained NPY and occasionally SOM and CGRP. It is suggested that NO may interact with a number of other messenger molecules to play a role both within the APG and IMG and also in the projection areas of the APG.
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PMID:Nitric oxide synthase, choline acetyltransferase, catecholamine enzymes and neuropeptides and their colocalization in the anterior pelvic ganglion, the inferior mesenteric ganglion and the hypogastric nerve of the male guinea pig. 949 65

Neuropeptide Y (NPY) and catecholamines are synthesized in response to stress. Adrenal NPY mRNA and tyrosine hydroxylase (TH) mRNA were measured by Northern analysis 2 h after a single 20 min bout of shaker stress in exercised and sedentary male Sprague-Dawley rats. Long-term exercise (18 weeks of voluntary wheel running) alone did not significantly alter adrenal NPY mRNA or TH mRNA levels. However, increases in stress-induced NPY and TH mRNA abundances were significantly enhanced by long-term exercise (P < 0.01). These results suggest that long-term physical activity may enhance the ability to synthesize NPY and catecholamines under conditions of stress.
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PMID:Response of rat adrenal neuropeptide Y and tyrosine hydroxylase mRNA to acute stress is enhanced by long-term voluntary exercise. 953 Sep 34

Nerve injury can lead to sympathetically dependent neuropathic pain. A possible site of sympathetic-sensory interaction is the dorsal root ganglion (DRG), where sympathetic axons form pericellular 'baskets' around a subpopulation of DRG neurons. Since these structures possibly represent functional units of sympathetic pain, we attempted to characterize the neuropeptidergic phenotype of basketed DRG neurons. We performed double-labeling immunohistochemistry for tyrosine hydroxylase and neuropeptides on DRG sections, 2 weeks following L5 spinal nerve ligation (a well-characterized animal model of sympathetic pain). We found that basketed DRG neurons typically do not contain substance P, calcitonin gene-related peptide, galanin, neuropeptide tyrosine, or vasoactive intestinal polypeptide, and we conclude that if sympathetic baskets contribute to neuropathic pain, the involvement of these neuropeptides is unimportant.
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PMID:Sympathetic axons surround neuropeptide-negative axotomized sensory neurons. 980 25


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