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)

With its abundance of neurons and immunocytes, the gut is a potentially important site for the study of the interaction between the nervous and immune systems. Using immunohistochemical techniques, we tested the hypothesis that gut-associated lymphoid tissue in the porcine small intestine might receive catecholaminergic, cholinergic and peptidergic innervation. Antibodies against protein gene product (PGP) 9.5 were employed to detect neuronal membranes; antibodies against tyrosine hydroxylase (TH), type 2 vesicular monoamine transporter (VMAT-2) and choline acetyltransferase (ChAT) were used to detect catecholaminergic and cholinergic neurons; and antibodies to neuromedin U-8 (NMU-8), substance P (SP) and vasoactive intestinal peptide (VIP) were also used. PGP9.5-immunoreactive nerve fibers were observed between jejunal Peyer's patch (PP) follicles and in submucosal ganglia localized at the base of continuous ileal PP. Many ChAT-positive and a few TH-/VMAT-2-immunoreactive neurons or axons adjacent to jejunal and ileal PP were observed. Neurons and fibers from ganglia situated between or at the base of PP follicles manifested robust immunoreactivities to VIP and NMU-8; relatively less SP immunoreactivity was observed at these locations. All neuromedin-U 8-positive neurons observed exhibited immunoreactivity to ChAT as did some VIP-positive neurons. The specific chemical coding of enteric neurons in close apposition to jejunal and ileal PP and the differential localization of neuropeptides within the jejunal and ileal PP are indicative of neuroimmunomodulation at these sites.
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PMID:Catecholaminergic, cholinergic and peptidergic innervation of gut-associated lymphoid tissue in porcine jejunum and ileum. 1057 Nov 16

The innervation of the human adrenal gland and of cortical lesions was studied in sections of cortical tissue (n=10), hyperplastic cortical tissue (n=3), and tissue from cortical adenomas (n=5) and carcinomas (n=6). The presence and distribution of nerve structures containing neuronal markers indicating sympathetic and parasympathetic innervation were studied by immunohistochemistry and the co-existence and co-localization patterns of the different markers by immunofluorescence. The cortex and hyperplastic cortical tissue had a moderate to rich supply of nerve structures containing the typical neuronal markers: protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), small vesicle synaptic protein type 2 (SV2), and nerves showing immunoreactivity to the adrenergic marker tyrosine hydroxylase (TH). All these immunoreactive nerves were located predominantly adjacent to blood vessels, but also among parenchymal cells. The cortex showed numerous nerve structures containing the neuropeptide substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal protein (VIP), but few nerves containing these peptides were seen in hyperplastic cortical tissue. Typical markers were occasionally observed in cortical adenomas but were not found in carcinomas, except in a few cases where PGP 9.5 and NSE were present, but only adjacent to necrotic areas. Nerves containing NPY and VIP occurred in varying numbers in both adenomas and carcinomas. NPY- and VIP-immunoreactive nerve structures were seen mostly alongside blood vessels. There were several types of co-existence. For instance, NSE/VIP-, TH/VIP- and TH/NPY-immunoreactive nerve structures were often seen in the same trunk, but were only partly co-localized.
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PMID:Innervation of human adrenal gland and adrenal cortical lesions. 1062

Small round cell tumors of childhood can be histologically ambiguous, can require tumor markers for an accurate diagnosis, and include neuroblastoma, peripheral primitive neuroectodermal tumor (pPNET), Ewing's sarcoma (ES), lymphoma, and rhabdomyosarcoma. Because the cell type of origin for ES remains controversial, characterizing gene expression in ES can provide diagnostic markers and lead to better understanding of tumor biology. We studied RNA expression of the neuronal genes protein gene product 9.5 (PGP 9.5) and tyrosine hydroxylase (TH) by Northern analysis in cell lines and tissue from small round cell tumors. PGP 9.5 showed strong expression in 17 of 17 neuroblastoma cell lines, 9 of 9 pPNET cell lines, and 11 of 11 ES cell lines. PGP 9.5 was weakly expressed in 1 of 1 alveolar rhabdomyosarcoma cell lines but not in 1 of 1 embryonal rhabdomyosarcomas, and weak expression was seen in 1 of 7 leukemia cell lines. In tumor tissue, all 12 neuroblastomas expressed PGP 9.5, as did all 7 pPNET and all 7 ES. PGP 9.5 was very weakly expressed in 6 of 9 rhabdomyosarcomas and 1 of 9 lymphomas. TH was expressed only in neuroblastomas, and no TH expression was seen in cell lines or tissue from other tumors. As high expression of PGP 9.5 was only found in neural tumors; PGP 9.5 expression by ES provides further evidence for a neural origin of this tumor, whereas TH expression is highly specific for neuroblastomas. PGP 9.5 expression should allow sensitive detection of minimal residual disease for ES and pPNET using reverse transcription-PCR, and the variability in TH and PGP 9.5 expression levels in neuroblastomas indicates that expression of both genes should be used for monitoring minimal residual disease by reverse transcription-PCR.
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PMID:Expression of protein gene product 9.5 and tyrosine hydroxylase in childhood small round cell tumors. 1069 May 38

We examined the expression of three neuropeptides that have been implicated in nociceptive transmission, and the sympathetic nerve fiber marker tyrosine hydroxylase, in 11 painful human Morton's neuromas, using immunohistochemistry. Antibodies against the neural markers RT97 and PGP 9.5 were used to map the general nerve fiber organization of the neuromas. Four specimens of normal human peripheral nerves were used as controls. Substance P, calcitonin gene-related peptide, and neuropeptide Y immunoreactivities were more pronounced in neuroma tissue than in control nerves. Neuropeptide immunofluorescence was seen both in larger nerve fiber trunks and in masses of disorganized axon profiles dispersed in loose connective tissue. Tyrosine hydroxylase immunoreactivity was present at varying levels of expression in neuroma nerve fiber trunks, in connective tissue nerve fiber bundles, and around some blood vessels. Our findings suggest that neuropeptides are involved in the response to injury in Morton's neuromas and that they could play a role in initiation or modulation of pain. In addition, pain from Morton's neuromas could be influenced by sympathetic nerve fibers.
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PMID:Neuropeptide- and tyrosine hydroxylase-immunoreactive nerve fibers in painful Morton's neuromas. 1091 58

The innervation of porcine testes was studied in intact animals and in boars undergoing active immunization against gonadotrophin-releasing hormone (GnRH) by means of immunohistochemistry using antibodies to tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H), vasoactive intestinal polypolypeptide (VIP), neuropeptide Y (NPY), synaptosome-associated protein of 25 kDa (SNAP-25) and protein gene product 9.5 (PGP 9.5). Moreover, the distribution of luteinizing hormone (LH) receptors in clusters of Leydig cells was also investigated. To identify these cells easily, either the NADPH-diaphorase histochemical technique or the Mayer counter-staining procedure was applied. Differences in the distribution pattern and relative density of particular subsets of intratesticular nerve fibres were observed in immunized boars as compared to those found in the intact animals. In the testes of non-treated animals, only single TH-immunoreactive (TH-IR) nerve fibres were observed. However, many D beta H-IR nerve terminals surrounded blood vessels in the tunica albuginea and parenchyma. Very scarce VIP-IR nerves occurred only in the tunica albuginea, mainly in close vicinity to blood vessels. Immunoreactivity to NPY occurred in single nerve fibres. Immunoreactivity to SNAP-25 and PGP 9.5 was found in single nerve fibres distributed mainly in the tunica albuginea. The interstitial cells were heavily stained for LH-receptors and NADPH-diaphorase. In the testes of immunized animals, only single TH-IR nerve fibres, scattered mainly in the tunica albuginea, were observed. Some TH-IR nerve terminals were also encountered in the parenchyma of the organ, where they were always associated with blood vessels. D beta H-IR nerve fibres formed a dense network distributed throughout the testis in association with the capsule, vasculature and interstitium. Some fibres were observed to run between seminiferous tubules. VIP-IR nerve fibres were located in the neighbourhood of blood vessels in the tunica albuginea and parenchyma. Only single VIP-IR nerves were found between seminiferous tubules. Numerous NPY-IR nerve fibres occurred in the tunica albuginea and parenchyma of the organ. SNAP-25-IR and PGP 9.5-IR nerve terminals formed a dense network distributed throughout the testis and many fibres were observed between seminiferous tubules. Interstitial cells were very weakly stained for LH receptors or NADPH-diaphorase.
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PMID:Has active immunization against gonadotrophin-releasing hormone any effect on testis innervation in the pig? An immunohistochemical study. 1100 73

Pregnancy induces transient and reversible denervation of the mammalian uterus and uterine artery which origin remains still unclear. It is well established that the density of sympathetic innervation is regulated by the levels of peptidergic diffusible growth factors, especially nerve growth factor (NGF). Whether a decrease of NGF and/or its signal-transducing receptor TrkA are involved in this physiological denervation of the uterine artery during pregnancy has not been analyzed. The aim of the present study is to analyze this topic on human uterine artery using ELISA, Western blotting and immunohistochemistry (associated to quantitative image analysis). The material was obtained from surgical pieces (hysterectomy) of non-pregnant and pregnant women from 4 to 16 weeks of gestation. The density of innervation for tyrosine hydroxylase assessed in whole mount samples of uterine artery, as well as the density of nerve fibers identified with other general nerve (PGP 9.5 and NFP) or Schwann cell (S-100 protein) markers was significantly reduced (p<0.05) in the uterine artery from pregnant woman. On the other hand, the tissular levels of NGF, the density of TrkA, and the immunostaining for both NGF and TrkA, were significantly reduced in uterine arteries from pregnant patients. These results strongly suggest that the physiological denervation occurring in the uterine artery during pregnancy is related to a decrease in the availability of NGF by nerve fibers, and to the impossibility to mediate its effect due to a remarkable decrease in the signal-transducing TrkA receptor.
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PMID:Pregnancy-induced denervation of the human uterine artery correlates with local decrease of NGF and TrkA. 1131 58

In the bird the carotid body is located between the distal (nodose) ganglion of the vagus nerve and the recurrent laryngeal nerve at the beginning of the common carotid artery, that is, the organ is located at the cervicothoracic border. The chicken carotid body receives numerous branches from the vagus and the recurrent laryngeal nerves. In addition, dense networks of the peptidergic nerve fibers immunoreactive for substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), galanin, and neuropeptide Y (NPY) are distributed in and around the carotid body parenchyma. The substance P- and CGRP-immunoreactive fibers are derived from both the superior and inferior ganglia of the vagus nerve. The VIP-, galanin-, and NPY-immunoreactive fibers originate from the 14th cervical ganglion of the sympathetic trunk. The endocrine organs including the thyroid gland, parathyroid glands, carotid body, and ultimobranchial gland are situated as a continuous series along the common carotid artery. The organs are supplied with arteries arising as one trunk from the common carotid artery. Glomus cells are widely distributed not only in the carotid body but also in the wall of the common carotid artery and around the common trunk and its branches. The glomus cells of the chicken carotid body exhibit intense immunoreactivity for serotonin, tyrosine hydroxylase, and chromogranin A. The cells located in the wall of the common carotid artery further express NPY mRNA and peptide. In the chickens exposed to isocapnic hypoxia for 35 days, 3-4-fold increase of the carotid body volume is induced and the carotid body glomus cells show enhanced synthetic and secretory activities. On the other hand, the cells in the wall of the common carotid artery display little changes after the long-term hypoxia, having different functions from the carotid body. The carotid body rudiment is formed in the lateral wall of the third branchial artery. The neural cells immunoreactive for TuJ1, PGP 9.5, and HNK-1, which are continuous with the inferior vagal (nodose) ganglion, first surround and then invade both the carotid body rudiment and the other portions of the third branchial artery, becoming glomus cells.
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PMID:Carotid body and glomus cells distributed in the wall of the common carotid artery in the bird. 1238 64

The aim of this investigation was to identify the proportional neurochemical codes of enteric neurons and to determine the specific terminal fields of chemically defined nerve fibers in all parts of the human gastrointestinal (GI) tract. For this purpose, antibodies against the vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), serotonin (5-HT), vasoactive intestinal peptide (VIP), and protein gene product 9.5 (PGP 9.5) were used. For in situ hybridization (35)S-labeled VMAT1, VMAT2, and VAChT riboprobes were used. In all regions of the human GI tract, 50-70% of the neurons were cholinergic, as judged by staining for VAChT. The human gut unlike the rodent gut exhibits a cholinergic innervation, which is characterized by an extensive overlap with VIPergic innervation. Neurons containing VMAT2 constituted 14-20% of all intrinsic neurons in the upper GI tract, and there was an equal number of TH-positive neurons. In contrast, DBH was absent from intrinsic neurons. Cholinergic and monoaminergic phenotypes proved to be completely distinct phenotypes. In conclusion, the chemical coding of human enteric neurons reveals some similarities with that of other mammalian species, but also significant differences. VIP is a cholinergic cotransmitter in the intrinsic innervation of the human gut. The substantial overlap between VMAT2 and TH in enteric neurons indicates that the intrinsic catecholaminergic innervation is a stable component of the human GI tract throughout life. The absence of DBH from intrinsic catecholaminergic neurons indicates that these neurons have a dopaminergic phenotype.
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PMID:Chemical coding of the human gastrointestinal nervous system: cholinergic, VIPergic, and catecholaminergic phenotypes. 1262 68

Vaginal function is strongly influenced by reproductive hormone status. Vaginal dysfunction during menopause is generally assumed to occur because of diminished estrogen-mediated trophic support of vaginal target cells. However, peripheral neurons possess estrogen receptors and are potentially responsive to gonadal steroid hormones. In the present study, we investigated whether sensory and autonomic innervation of the vagina varies among rats during the estrus phase of the estrous cycle, following chronic ovariectomy, and after sustained estrogen replacement. Relative to rats in estrus, ovariectomized rats showed a 59% elevation in nerve density, as determined using the panneuronal marker PGP 9.5. This increase persisted even after correcting for differences in vaginal tissue size, indicating true axonal proliferation after ovariectomy rather than changes secondary to altered volume. Increased total innervation after ovariectomy was attributable to increased densities of sympathetic nerves immunostained for tyrosine hydroxylase (70%), cholinergic parasympathetic nerves immunoreactive for vesicular acetylcholine transporter (93%), and calcitonin gene-related peptide-immunoreactive sensory nociceptor nerves (84%). Myelinated primary sensory innervation revealed by RT-97 immunoreactivity did not appear to be affected. Sustained 17beta-estradiol administration reduced innervation density to an extent comparable to that of estrus, implying that estrogen is the hormone mediating vaginal neuroplasticity. These findings indicate that some aspects of vaginal dysfunction during menopause may be attributable to changes in innervation. Increased sympathetic innervation may augment vasoconstriction and promote vaginal dryness, while sensory nociceptor axon proliferation may contribute to symptoms of pain, burning, and itching associated with menopause and some forms of vulvodynia.
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PMID:Estrogen regulates vaginal sensory and autonomic nerve density in the rat. 1518 32

The mutilated-foot rat (mf rat) is an autosomal recessive mutant with characteristic digit deformities in adult animals, and this phenotype mimics many aspects of human sensory neuropathy. The genetics of mf rats was recently elucidated. To understand whether the genotype is responsible for cutaneous denervation before clinically overt mutilation in adult mf rats, we investigated skin innervation in postnatal day 7 (P7) mf rats and compared the patterns with P7 wild-type rats. The mf rat carries a G-->A mutation in the gene encoding the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4). In the footpad skin of P7 mf rats, there was a >90% loss of epidermal nerves (0.7-7.9% of P7 wild-type rats) as indicated by neuronal markers including protein gene product 9.5 (PGP 9.5), growth-associated protein 43 (GAP43), calcitonin gene-related peptide (CGRP), and substance P (SP). The epidermis of hairy skin in hind feet was completely denervated in mf rats as well. Compared with an approximately 80% reduction in the size of dermal nerve fascicles and a parallel loss of nerve fibers, the nearly complete absence of epidermal innervation suggests further sensory nerve degeneration at the level of nerve terminals in the epidermis. In contrast, the loss of epidermal nerves in the abdominal skin of mf rats was less extensive than that in the footpad skin of mf rats; CGRP (+) and SP (+) fibers were moderately reduced (28.3-56.4% of levels of wild-type rats) with normal amounts of PGP 9.5 (+) and GAP43 (+) nerves. Sympathetic innervation as assessed by tyrosine hydroxylase immunoreactivity was absent from the footpad and abdominal skin of mf rats. In conclusion, there is regional skin denervation with diffuse sympathetic denervation in P7 mf rats. These results suggest that the mutation in Cct4 underlies cutaneous nerve degeneration in mf rats.
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PMID:Cutaneous and sympathetic denervation in neonatal rats with a mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 gene. 1519 90


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