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)

The innervation of human cerebral blood vessels has been examined using synaptophysin, a marker of synaptic vesicles, and chromogranin A, a marker of large dense-core vesicles. The catecholaminergic marker tyrosine hydroxylase was used for comparison. Synaptophysin and tyrosine hydroxylase demonstrated a similar distribution of nerve fibers whereas chromogranin A terminals were only sparsely evident. Our results suggest that there is not a subset of nerve fibers in existence which has a distribution different than that of catecholaminergic fibers. Furthermore, in view of its unexpected sparse distribution, chromogranin A in the nervi vasorum is not likely to be a significant contributor to cerebral blood flow regulation.
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PMID:Human cerebrovascular nerve fibers immunoreactive for synaptophysin, chromogranin A and tyrosine hydroxylase. 762 58

The present study was undertaken to define the temporal pattern and distribution of cells positive for chromogranin A (CgA) and tyrosine hydroxylase (TH) in various developmental stages of fetal bovine adrenal gland. CgA is an acidic protein, co-stored and co-released with amines and a variety of peptide hormones and neurotransmitters in dense core vesicles of neural and endocrine cells and can be used as a marker for these cells and their malignant counterparts. TH is the rate-limiting enzyme in catecholamine biosynthesis and reflects noradrenergic differentiation. The expression of CgA and TH was examined by immunohistochemistry. CgA immunoreactivity appears first in 35-day-old bovine fetuses. By the end of the second month, CgA-labelled cells are scattered throughout the entire primordium of the adrenal gland, and at a fetal age of 85-91 days most of these cells concentrate in the developing adrenal medulla. From this stage onwards, immunoreactive cells of the marginal zone of the medulla exhibit significantly stronger CgA immunoreaction than the central area. TH immunoreactivity appeared in the adrenal primordium for the first time at the end of the second month of gestation. The distribution pattern of TH-positive cells was similar to that described for CgA, and no significant differences in topographical arrangement between TH- and CgA-positive cells can be detected. The results show that bovine adrenal chromaffin cells express CgA already during their earliest stages of development and prior to TH. The stronger immunoreaction of marginal adrenal medullary cells suggests an adrenalcortical effect of glucocorticoids on the expression of CgA.
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PMID:Early expression of chromogranin A and tyrosine hydroxylase during prenatal development of the bovine adrenal gland. 772 91

Chromogranin A and B (CAB) occur in several peptide hormone-producing cells and in neurons of the brain. The aim of the present study was to investigate the possible neuronal localization of these chromogranins in the ganglionic and aganglionic bowel in Hirschsprung's disease by immunocytochemistry and radioimmunoassay, using antibodies recognizing either chromogranin A or both chromogranin A and B. Further, the coexistence of chromogranins and other neuronal constituents was studied. CAB were found in nerve fibers and occasionally in nerve cell bodies of submucous and myenteric ganglia in the ganglionic bowel, indicating that at least a population of chromogranin-immunoreactive nerve fibers is intrinsic in origin. CAB-immunoreactive fibers were numerous in the muscle layers of the aganglionic segment. These fibers contained tyrosine hydroxylase (TH), which indicates that they are adrenergic, in both ganglionic and aganglionic bowel. In the muscle layers of aganglionic (but not ganglionic) bowel, chromogranin A coexisted with galanin, neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP). The concentration of CAB in smooth muscle specimens was higher in the aganglionic bowel than in the ganglionic bowel. Thus, chromogranins are present in the human enteric gut hyperinnervating the aganglionic bowel of Hirschsprung's disease.
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PMID:Chromogranin A and B in neuronal elements in Hirschsprung's disease: an immunocytochemical and radioimmunoassay study. 780 11

A number of neuroendocrine and neuronal markers were demonstrated in Leydig cells of the testes of 18 men aged between 20 and 81 years. Tissue sections were divided into five groups, i.e. carcinoma of the prostate (control cases; n = 4), seminoma (n = 8), anti-androgen therapy (n = 3), oestradiol therapy (n = 2) and cryptorchidism (n = 1). The following substances were immunocytochemically tested: the monoamine synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase, the indolamine serotonin, the calcium-binding proteins parvalbumin, calbindin and S-100 protein, the microtubule associated protein-2, as well as neurofilament protein 200, synaptophysin, neuron specific enolase, substance P and chromogranin A + B. All these substances were found in Leydig cells of all sections independently of the pathological changes of the testes. Compared with the control cases, all the other groups showed a significantly weaker immunoreactivity for all markers. The uniformity of staining among the different antibodies allows the deduction that these neuroactive peptides may belong to a basic equipment of Leydig cells probably stabilizing their function in an autocrine manner. On the other hand, Leydig cells themselves seem to be a stable structural component of the testis, which are not essentially involved in the pathogenesis of the disturbances mentioned above.
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PMID:Neuroendocrine marker substances in human Leydig cells--changes by disturbances of testicular function. 790 79

Chromogranins are a family of acidic proteins known to occur in the secretory granules of endocrine cells and neurons in mammals. The aim of the present study was to investigate the possible neuronal localisation of chromogranins in human intestine and their relationship with other neuronal constituents using one antibody recognizing both chromogranin A and B (CAB) and others recognizing only chromogranin A. Immunoreactive CAB was found to occur in mucosal endocrine cells and in neuronal elements of all layers throughout human gut. A few to large number of CAB-immunoreactive nerve fibers were seen in smooth muscles as well as in submucous and myenteric ganglia and they were regularly found around blood vessels. Occasional CAB immunoreactive nerve cell bodies could be demonstrated in both submucous and myenteric ganglia indicating a local origin of some of the immunoreactive fibers. Most of these neurons seemed to lack acetylcholine esterase, and could be classified as non-cholinergic. CAB coexisted with the catecholamine-synthesizing enzyme tyrosine hydroxylase indicating the presence of chromogranins in noradrenergic nerve fibers. The presence of CAB-immunoreactive nerve cell bodies indicates that some CAB-containing fibers are intrinsic in origin. The distribution of chromogranin A and B immunoreactive nerve fibers in all layers of the gut wall suggests multiple targets for neuronal CAB, and/or their processing products.
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PMID:Immunocytochemical evidence for chromogranin A and B in neuronal elements in human gut. 793 7

Previous investigations have demonstrated that adrenal chromaffin cells survive poorly when grafted into the striatum of rodents, nonhuman primates, and patients with Parkinson's disease. This poor survival has been attributed to the low levels of endogenous NGF within the striatum. However, chromaffin cells isolated from the nonchromaffin constituents of the adrenal medulla (fibroblasts and endothelial cells) have recently been demonstrated to survive grafting into a number of CNS sites. The present study determined whether nonchromaffin constituents of the adrenal medulla may be responsible for poor graft survival. We compared the survival of intrastriatally grafted isolated bovine chromaffin cells with that observed following implantation of either perfused adrenal medullary suspensions containing all adrenal medullary cell types or isolated chromaffin cells that were then reseeded with autologous fibroblasts and endothelial cells. Implants of perfused adrenal medullary cells survived poorly and most graft sites were infiltrated with macrophages. The chromaffin cells in this group that did survive appeared to be in the process of degeneration. In contrast, large numbers of isolated chromaffin cells survived for up to 2 months following transplantation. These cells maintained their endocrine phenotype and stained for all enzymatic markers of catecholamine synthesis as well as chromogranin A. Morphologically, these cells resembled chromaffin cells seen in situ and the perigraft region was essentially devoid of macrophages. When isolated chromaffin cells were reseeded with autologous fibroblasts and endothelial cells, the implants degenerated and few, if any, surviving chromaffin cells were observed. Interestingly, these latter grafts induced a host-derived sprouting response of tyrosine hydroxylase-immunoreactive fibers. These data demonstrate that large numbers of adrenal chromaffin cells can survive intrastriatal implantation in the absence of exposure to exogenous NGF. Rather, the nonchromaffin cells of the adrenal medulla (fibroblasts and endothelial cells) appear to compromise the viability of grafted chromaffin cells. Once they are eliminated from the graft, robust survival of chromaffin cells occurs. If clinical trials employing adrenal medullary grafts are still to be considered for the treatment of Parkinson's disease, isolation of the chromaffin cells should be considered to enhance graft viability.
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PMID:Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability. 810 42

The omentum, a rich source for trophic and angiogenic factors, was explored as a potential intermediate transplant site to facilitate long-term survival of chromaffin tissue. Autologous rat adrenal medullas were grafted into omental pockets. All grafts became densely vascularized. The grafted chromaffin tissue exhibited strong immunoreactivities for tyrosine hydroxylase, synaptophysin and chromogranin A throughout the observation period of 16 weeks. The expression of these markers implies that grafted chromaffin cells retained the key enzyme for catecholamine biosynthesis and the organelles required for catecholamine secretion. Moreover, intermediate transplant of chromaffin tissue to the omentum could provide a favourable conditioning microenvironment thus augmenting the potential for survival of functional chromaffin tissue.
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PMID:Long-term survival of autologous adrenal medulla grafts in the great omentum of the rat. 810 7

Despite the pivotal clinical significance of the human anal canal, little is known about its total and specific innervation. This study assessed the comparative distribution and histotopology of nerve fibres immunoreactive for neural markers and a variety of regulatory active neuropeptides in the human anal canal by light microscopic immunohistochemistry. Depending on the epithelial zone and region of the anal canal, the neural elements were differentially immunoreactive for the pan-neural marker protein gene product 9.5, the catecholamine marker tyrosine hydroxylase, the neuroendocrine marker chromogranin A, and various neuropeptides. Protein gene product 9.5-immunoreactive nerve fibres were ubiquitously abundant in the anal canal. In the anal transitional zone, ectopic epithelial types were supplied by the same pattern of peptidergic nerves as the respective type of epithelium in normotopic location. In the dermis of the squamous zone and in the perianal epidermis, unusual distribution patterns of nerve fibres, referred to as areas of high nerve fibre density, were encountered. Double immunohistochemistry revealed region-specific coexistence patterns of neuropeptidergic nerve fibres, and novel peptide coexistence patterns were detected in anal nerve fibres. Subsets of nerve fibres formed close spatial relationships with chromogranin A-positive neuroendocrine cells, most frequently in the anal transitional zone. Chromogranin-A positive cells were shown to be present in the epithelium of perianal eccrine sweat glands. The differential distribution, peptide phenotypes and coexistence patterns of different nerve fibre populations in the human anal canal may reflect topospecific regulatory functions of neurally released neuropeptides in health and disease.
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PMID:Regional specificities in the distribution, chemical phenotypes, and coexistence patterns of neuropeptide containing nerve fibres in the human anal canal. 822 26

A number of marker substances for neuronal and neuroendocrine cells have been demonstrated in the cytoplasm of the interstitial Leydig cells of human testes using basic immunocytochemical methods and some of their modifications. We were able to reveal immunoreactivity for enzymes involved in the synthesis of the catecholamines dopamine and noradrenaline (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase), for the indolamine 5-hydroxytryptamine (serotonin), as well as for a number of well-known neuronal markers such as the neurofilament protein 200, synaptophysin, chromogranin A + B, the neural cell-adhesion molecule (N-CAM), the microtubule-associated protein (MAP-2), and the calcium-binding proteins: S-100, calbindin and parvalbumin. Immunoreactivity for these substances was found in the majority of the interstitial cells although differences in the staining intensity among the individual Leydig cells and among Leydig cells from different patients were observed. At the electron-microscopic level the Leydig cell cytoplasm was seen to contain microtubules, intermediate- and microfilaments as well as clear (40-60 nm) and dense-core (100-300 nm) vesicles, providing a morphological correlate for some of the immunocytochemical results. Although individual marker substances are not absolutely specific for nerve and neuroendocrine cells, the results obtained, together with the already established neuron-specific enolase-, substance P-, methionine-enkephalin- and proopiomelanocortin (POMC)-derived peptide-like immunoreactivity, provide strong evidence for the neuroendocrine (paraneuronal, APUD-like) nature of the Leydig cells of the human testis.
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PMID:The Leydig cell of the human testis--a new member of the diffuse neuroendocrine system. 847 1

Bovine chromaffin cell cultures were treated with either reserpine or alpha-methyl-p-tyrosine for up to 10 days. Afterwards the cells were harvested and the degree of proteolytic processing of secretogranin II, chromogranin A and chromogranin B was determined by immunoblotting and HPLC followed by RIA. There was a significant increase in the proteolysis of all three chromogranins after 4-6 days in the presence of reserpine. The small peptides formed in the presence of reserpine in vitro are also produced in vivo. A similar effect was observed with alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, but the response took up to 10 days to develop. Both drugs decreased catecholamine levels but reserpine was more effective, reaching a high degree of depletion after 4 days. In addition, experiments in vitro indicate that low millimolar amounts of either adrenaline (IC50 5.2 mM) or noradrenaline (IC50 2.4 mM) can significantly impair the proteolytic activity of recombinant murine prohormone convertase 1 when assayed with synthetic fluorogenic and/or peptidyl substrates. We conclude that a lowering of catecholamine levels in chromaffin granules leads to a concomitant increase in proteolytic processing of all secretory peptides. Apparently within chromaffin granules the endoproteases are inhibited by catecholamines and thus their removal leads to increased proteolysis.
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PMID:Processing of chromogranins in chromaffin cell culture: effects of reserpine and alpha-methyl-p-tyrosine. 867 Jan 75


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