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)

Respiratory tract nerves have cell bodies outside (sensory, sympathetic) and inside (parasympathetic) the organ and contain bioactive peptides. These include calcitonin gene-related peptide and tachykinins (sensory nerves), vasoactive intestinal polypeptide (parasympathetic nerves), and neuropeptide with tyrosine (sympathetic nerves). Because transplantation interrupts the extrinsic nerve supply to the tissues, we have examined transplanted human respiratory tracts (n = 11) removed at retransplantation 2 to 42 months after the primary transplant in order to determine whether any nerves and peptide synthesis persist. As controls to establish nerve distribution in human respiratory tract, tissues were obtained from 10 lung resections and five autopsies. Cryostat sections were immunostained to demonstrate the general neural marker PGP 9.5, neuropeptides, and the catecholamine-synthesizing enzyme tyrosine hydroxylase. Nerves immunoreactive for PGP 9.5 were detected in all transplanted tissues. They were fewer in number overall than in control tissue, significantly so in epithelium of trachea and bronchus where they were present sparsely in only three cases. Nerves immunoreactive for tyrosine hydroxylase were significantly fewer in the transplants. Peptide-immunoreactive nerves were also reduced in number in the transplants, except for vasoactive intestinal polypeptide, which was only significantly changed in blood vessels in the lung. Ganglion cells immunoreactive for tyrosine hydroxylase and neuropeptide with tyrosine were seen in the transplanted tissues in five cases, but never in the control tissues. We conclude that whereas some nerves and neuropeptide synthesis persist after extrinsic pulmonary denervation, potentially significant changes also occur, including the appearance in intrinsic parasympathetic neurones of immunoreactivity for a catecholamine-synthesizing enzyme and a peptide normally found in sympathetic nerves.
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PMID:Persistence of intrinsic neurones and possible phenotypic changes after extrinsic denervation of human respiratory tract by heart-lung transplantation. 197 6

This immunohistochemical study of nerves in the synovial tissue of Sprague-Dawley rats demonstrated the occurrence of 4 neuropeptides and 2 enzymes that are involved in the synthesis of catecholamines. Substance P and calcitonin gene-related peptide were colocalized in fibers that terminated as varicosal endings in the synoviocyte layer. Similarly, tyrosine hydroxylase and dopamine beta-hydroxylase, which reflect the presence of noradrenaline, were colocalized with neuropeptide Y. These fibers were predominantly found adjacent to and within blood vessel walls. Immunoreactivity to vasoactive intestinal polypeptide was seen in varicose nerve terminals in the synoviocyte layer. Many were localized in vessel walls. There is accumulating evidence of an involvement of substance P and noradrenaline in the pathogenesis of inflammatory joint disease and nociception. The role of these colocalized neuropeptides, namely, calcitonin gene-related peptide and neuropeptide Y, in the pathophysiology of such conditions warrants further analysis.
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PMID:Noradrenergic and peptidergic nerves in the synovial membrane of the Sprague-Dawley rat. 197 38

Bronchial reactivity changes during childhood, indicating possible changes in neural control. Nerves supplying the intrapulmonary airways were therefore studied in autopsy tissue from 14 normal infants (0 to 3.5 yr), 3 children (8.3 to 10.75 yr), and 4 adults (17 to 24 yr). An indirect immunofluorescence technique was used to study the distribution and relative number of nerve fibers containing the general neuronal markers protein gene product 9.5 and synaptophysin. Nerve subpopulations were identified using antisera to neuropeptide tyrosine, vasoactive intestine polypeptide, somatostatin, substance P, calcitonin gene-related peptide, and the enzyme tyrosine hydroxylase. Between birth and 3 yr, the distribution and relative number of immunoreactive nerves shown by both the general neuronal markers and specific antisera did not change. Neuropeptide tyrosine-immunoreactive nerves were the most common peptide-containing nerve subpopulation identified in the human lung, supplying bronchial smooth muscle, submucosal glands, cartilage, and submucosa. Other peptide-containing nerves exhibited distinct distribution patterns. Two differences in the airway innervation were identified between cases aged 0 to 3.5 yr and the older age groups. Relatively fewer peptide-containing nerves occurred in the adult bronchioli and respiratory unit, but the relative number of vasoactive intestinal polypeptide-containing nerves supplying the bronchial and bronchiolar smooth muscle was greater in the two older age groups. Given these apparent age-related differences in the number of peptide-containing nerves supplying the human airway, studies on the development of peptide receptors are indicated.
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PMID:Immunohistochemical localization of peptide-containing nerves in human airways: age-related changes. 197 91

In this study the effect of long-term selective sensory vs. sympathetic denervation was examined in the rat lung. Immunoreactivities for calcitonin gene-related peptide (CGRP) on the one hand and tyrosine hydroxylase (TH) on the other, were used as indexes to assess the changes in the two nerve systems. Following long-term chemosympathectomy a marked increase of CGRP-immunoreactive nerve fibers was seen in the sections, while TH-immunoreactive nerve fibers appeared depleted. Inversely, long-term sensory denervation resulted in an increase of TH-immunoreactive nerve fibers with a sharp decrease of CGRP-immunostained fibers. These results suggest a peripheral interaction between these innervation systems in the lung, the mechanism of which has still to be elucidated.
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PMID:Effects of long-term sensory vs. sympathetic denervation on the distribution of calcitonin gene-related peptide and tyrosine hydroxylase immunoreactivities in the rat lung. 197 50

Cranial and spinal sensory ganglia of the guinea-pig were investigated by means of histochemistry and biochemistry for the presence of catecholamines and catecholamine-synthesizing enzymes. Sensory neurons exhibiting immunoreactivity to the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase (TH), were detected by immunohistochemistry in lumbo-sacral dorsal root ganglia, the nodose ganglion and the petrosal/jugular ganglion complex. The carotid body was identified as a target of TH-like-immunoreactive (TH-LI) neurons by the use of combined retrograde tracing and immunohistochemistry. Double-labelling immunofluorescence revealed that most TH-LI neurons also contained somatostatin-LI, but TH-LI did not coexist with either calcitonin gene-related peptide- or substance P-LI. TH-LI neurons did not react with antibodies to other enzymes involved in catecholamine synthesis, i.e., aromatic amino acid decarboxylase (AADC), dopamine-beta-hydroxylase (D beta H), and phenylethanolamine-N-methyl-transferase (PNMT). Petrosal neurons as well as their endings in the carotid body lacked dopamine- and L-DOPA-LI. Sensory neurons did not display glyoxylic acid-induced catecholamine fluorescence. Ganglia containing TH-LI neurons were kept in short-term organ culture after crushing their roots and the exiting nerve in order to enrich intra-axonal transmitter content at the ganglionic side of the crush. However, even under these conditions, catecholamine fluorescence was not detected in axons projecting peripherally or centrally from the ganglia. Sympathetic noradrenergic nerves entered the ganglia and terminated within them. Accordingly, biochemical analyses of guinea-pig sensory ganglia revealed noradrenaline but no dopamine. In conclusion, catecholamines within guinea-pig sensory ganglia are confined to sympathetic nerves, which fulfill presently unknown functions. The TH-LI neurons themselves, however, lack any additional sign of catecholamine synthesis, and the presence of enzymatically active TH within these neurons is questionable.
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PMID:Catecholamines and catecholamine-synthesizing enzymes in guinea-pig sensory ganglia. 197 3

The peptidergic innervation of guinea-pig coronary arteries was investigated by means of immunohistochemical, ultrastructural and in vitro pharmacological techniques. A network of nerves was demonstrated in all major epicardial arteries by means of an antiserum to the neuronal marker protein gene product 9.5. The majority of nerve fibres possessed neuropeptide Y (NPY) and tyrosine hydroxylase (TH) immunoreactivity, the number and distribution of nerves immunoreactive for NPY being similar to that of nerves containing TH immunoreactivity. Numerous nerve fibres displaying immunoreactivity for substance P, neuropeptide K and calcitonin gene-related peptide (CGRP) were also found. In double-stained preparations substance P immunoreactivity was co-localized with CGRP and with neuropeptide K immunoreactivities in the same varicose nerve fibres. Ultrastructural studies revealed the presence of numerous axon varicosities at the adventitial-medial border. NPY immunoreactivity was localized in large granular vesicles in nerve varicosities which also contained numerous small granular vesicles. Large granular vesicle-containing nerves also displayed immunoreactivity for dopamine-beta-hydroxylase. With an in vitro method, the vasomotor responses to perivascular peptides were characterized in epicardial and intramyocardial arteries. In epicardial arteries neither noradrenaline nor NPY elicited a contractile response. Only in some intramyocardial arteries was an NPY-mediated contraction demonstrated. No potentiating effect of noradrenaline and NPY was observed in either epicardial or intramyocardial arterial segments. In contrast, CGRP, substance P and vasoactive intestinal peptide (VIP) all produced a concentration-dependent relaxation of both epicardial and intramyocardial arteries. These results suggest that peptide-containing nerves associated with guinea-pig coronary arteries may predominantly be involved in mediating vasodilation.
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PMID:Peptide-containing nerve fibres in guinea-pig coronary arteries: immunohistochemistry, ultrastructure and vasomotility. 198 Dec 17

Many neurotransplantation studies have dealt with the ability of solid fetal spinal grafts to develop in the previously traumatized spinal cord of a host. In neurodegenerative spinal diseases, however, motoneuronal death occurs in the absence of a trauma, i.e., in the absence of axotomy of afferent fibers. Lesioning the spinal cord with an excitotoxic agent may provide a useful neurodegenerative model. The present study has been undertaken to determine whether homotypic fetal neurons transplanted as a cell suspension are able to rebuild a neural circuitry. Emphasis is given here to the analysis of the development of transplanted motoneurons and host-graft connectivity. The lesion was made by kainic acid on the right side of the lumbar enlargement 1 week before transplantation. The fetal spinal cords were taken from rat embryos (gestational day E12-13) and transplanted as cell suspensions. Light- and electron-microscopic analysis demonstrated that the excitotoxic lesion extended over the entire spinal segment and was confined primarily to the ventral and intermediate horns, implying the death of all motoneurons with consequent paralysis and muscular atrophy of corresponding hindlimb. The lesion was characterized by a lack of neurons, glial proliferation, and sparing of fibers of passage and afferents. Two to fourteen months after surgery, the transplants were generally large, occupying most of the neuron-depleted area. The boundaries between the transplant and host tissue were clearly delineated by the higher cellular density of the graft and the particular cytoarchitecture, i.e., the cell suspension grafts did not display a laminar organization. Among the different neuronal populations within the transplant, one resembled motoneurons: large, typically Nissl-stained and immunoreactive for calcitonin gene-related peptide (CGRP). No grafted neuron, however, extended an axon into the host ventral roots. Monoaminergic afferents from the host were studied using immunostaining for serotonin, noradrenaline, and tyrosine hydroxylase. These afferent fibers, thin and varicose, grew for a long distance and formed a network within transplants. Similarly, primary sensory CGRP-immunoreactive fibers (entering the graft from the dorsal host-graft interface) penetrated deeply into transplants. The response of cortico- and rubro-spinal afferents to the implantation of fetal tissue was different. After injection of WGA-HRP, a few anterogradely labeled cortical and rubral fibers entered only the most peripheral portion of transplants. In conclusion, our results indicate that fetal spinal neurons can be successfully transplanted into the adult neuron-depleted spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Homotypic fetal transplants into an experimental model of spinal cord neurodegeneration. 227 98

Seven patients (6 women, 1 man) with severe idiopathic chronic constipation, who underwent surgery with subtotal colectomy and ileorectal anastomosis, were investigated for the occurrence and density of nerve fibres, immunoreactive to different neuropeptides in the mucosa, submucosa, ganglia and smooth muscle in fresh specimens from the colon ascendens, the colon transversum and the colon descendens-sigmoideum. The following substances were studied: enkephalin, substance P, somatostatin, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide, bombesin, motilin, tyrosine hydroxylase, dynorphin and galanin. Nerve fibres immunoreactive to CGRP occurred in large numbers in the myenteric ganglia of the patients with severe idiopathic chronic constipation, whereas in the myenteric ganglia of the control cases they only occurred in low numbers. In two patients there was no detectable motilin immunoreactivity and in one patient only sparse in the mucosa and the smooth muscle. The other neuropeptides investigated occurred in the density and distribution previously reported in the normal gut. With the present technique there were indications that patients with severe idiopathic chronic constipation have a significant difference in the occurrence of immunoreactive nerve fibres to CGRP and motilin compared to control patients.
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PMID:Slow transit chronic constipation (Arbuthnot Lane's disease). An immunohistochemical study of neuropeptide-containing nerves in resected specimens from the large bowel. 228 99

The ovary is innervated by noradrenergic and peptidergic fibers. Treatment of neonatal rats with antibodies to nerve growth factor (NGF Ab) resulted in failure of the sympathetic (noradrenergic and neuropeptide-Y) nerves to develop. Partial loss of sensory innervation, represented by calcitonin gene-related peptide fibers, was also observed. Follicular growth was stunted, and production of androgens and estradiol was reduced. The timing of first ovulation was delayed, estrous cyclicity was disrupted, and fertility was compromised. Plasma LH levels were elevated, and LH pulsatility was enhanced, suggesting primary ovarian failure. A normal appearance of tyrosine hydroxylase-, LHRH-, and neuropeptide-Y-immunoreactive neurons in the hypothalamus, as determined by immunocytochemistry, suggested that neonatal immunosympathectomy did not directly affect hypothalamic reproductive function. In vitro release of LHRH from median eminence nerve terminals in response to prostaglandin E2 was, however, reduced in NGF Ab-treated rats. Normalization of the response by prior in vivo exposure of the animals to physiological estradiol levels, suggested that the diminished LHRH output was due at least in part to estrogen deficiency. Although ovarian dysfunction induced by immunosympathectomy may be related to alterations in vascular tone, the striking loss of perifollicular noradrenergic innervation caused by NGF Ab suggests that the absence of the nonvascular norepinephrine stimulus to follicular steroidogenesis is a primary factor responsible for the alterations observed. The results indicate that development of the sympathetic innervation of the ovary is NGF dependent and that NGF, by supporting the differentiation and survival of the innervating neurons, contributes to the acquisition of mature ovarian function.
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PMID:Involvement of nerve growth factor in female sexual development. 229 94

Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide.
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PMID:Immunohistochemical demonstration of human cardiac innervation before and after transplantation. 231 94


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