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)

Administration of the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces a parkinsonian syndrome in primates. Intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the common marmoset (Callithrix jacchus) produced symptoms of rigidity, akinesia and tremor which persisted for at least one month. However, after this time, considerable behavioural recovery occurred, although animals were still severely bradykinetic compared with controls. Marmosets were allowed to survive for 1, 3 1/2 or 7 months prior to histological and immunocytochemical analysis. Detection of catecholaminergic neurons using antibodies directed against the enzyme tyrosine hydroxylase revealed a profound (80%) loss of dopaminergic cells from the substantia nigra one month after initiation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. This was accompanied by a severe gliosis. Fewer cells were lost from the adjacent ventral tegmental area (45%), but dopamine-containing cells in other brain areas were not obviously affected. At longer survival times the substantia nigra was less damaged, with a proliferation of glia in the pars compacta and a loss of approximately 20% of the dopaminergic perikarya. Using immunohistochemical techniques, the distribution of neuropeptides substance P, [Met]enkephalin and dynorphin 1-17-like immunoreactivity were examined and found to exhibit distinctive patterns in the marmoset substantia nigra. The integrity of these systems appeared intact at all times after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. These results support the hypothesis that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces a clinical syndrome, indistinguishable from Parkinson's disease, via a selective destruction only of neurons with perikarya in the substantia nigra pars compacta and the ventral tegmental area. The findings that the peptidergic input to these cells together with most non-nigral dopaminergic cell groups are not damaged, indicate that the selectivity of the lesion produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine appears greater than that seen in idiopathic Parkinson's disease. The neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset may not be permanent since both behavioural and biochemical recovery were observed after several months.
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PMID:An immunohistochemical study of the acute and long-term effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset. 289 93

The motor-activating effects of rimorphin, an opioid peptide derived from prodynorphin, were examined in the substantia nigra pars reticulata of rats. Unilateral microinjections of rimorphin produced dose-dependent contralateral rotational behavior that was antagonized by naloxone, suggesting that these effects were mediated by opiate receptors. Lesions of midbrain dopamine cells with 6-hydroxydopamine (6-OHDA) produced a 95% or greater depletion of tyrosine hydroxylase in the striatum ipsilateral to the lesion, but failed to reduce the number of circles made by the rats. In addition to an overall preservation of rimorphin-induced circling in animals with 6-OHDA lesions, 50% of these rats exhibited circling that was at least 2 standard deviations above the mean of animals without lesions. The motor activating effects of rimorphin, thus, appear to occur independently of the nigrostriatal dopamine system; these effects may instead be mediated by GABAergic efferents in the pars reticulata.
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PMID:Dopamine-independent motor behavior following microinjection of rimorphin in the substantia nigra. 289 62

The laterodorsal tegmental nucleus (ntdl) contains a cluster of cells located just medial to the locus coeruleus in the pontine brainstem. The ntdl has been shown to project both rostrally to the forebrain and diencephalon and caudally to the spinal cord. In an effort to characterize this region neurochemically, the present study was conducted to identify a variety of neurochemicals localized within perikarya and fibers of the ntdl and surrounding nuclei. Rats were perfused with formalin, and brain sections were processed for fluorescence immunocytochemistry and acetylcholinesterase (AChE). Of the neurochemicals screened, atrial natriuretic factor (ANF), choline acetyltransferase (ChAT), cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), dynorphin B (Dyn B), galanin, somatostatin, substance P, neurotensin (NT), neuropeptide Y (NPY), vasopressin, vasoactive intestinal polypeptide (VIP), serotonin (5HT), glutamic acid decarboxylase (GAD), and tyrosine hydroxylase (TH) were studied. AChE and ChAT staining revealed that the ntdl contains mostly cholinergic neurons. In addition, brightly reactive substance P and galanin and paler staining CRF, ANF, CGRP, NT, VIP, and Dyn B cell bodies were found within the ntdl. Varicose fibers in this nucleus also contained these peptides in addition to CCK, GAD, TH, 5HT, and NPY. The dorsal tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and the parabrachial region contained a dense and varied assortment of peptides with distinct positions and patterns. This multiplicity of neurochemicals within this area suggests a possible influence on a variety of functions modulated by the ntdl and other closely associated tegmental nuclei.
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PMID:Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area. 289 81

The hypothalamus provides a major projection to the spinal cord that innervates primarily lamina I of the dorsal horn and the sympathetic and parasympathetic preganglionic cell columns. We have examined the chemical organization of the neurons that contribute to this pathway by using combined retrograde transport of fluorescent dyes and immunohistochemistry for 15 different putative neurotransmitters or their synthetic enzymes. Our results demonstrate that 5 cytoarchitectonically distinct cell groups in the hypothalamus contribute to the spinal projection and that each has its own predominant chemical types. In the paraventricular nucleus, substantial numbers of hypothalamo-spinal neurons stain with antisera against arginine vasopressin (25-35%), oxytocin (20-25%), and met-enkephalin (10%). About 25% of the neurons with spinal projections in the retrochiasmatic area stain with an antiserum against alpha-melanocyte-stimulating hormone. Nearly 100% of the hypothalamo-spinal neurons in the tuberal lateral hypothalamic area stain with this same antiserum, but these cells do not stain for other proopiomelanocortin-derived peptides, and so probably contain a cross-reacting peptide. This population must be distinguished from an adjacent cell group, in the perifornical region, where many spinal projection neurons stain with antisera against dynorphin (25%) or atrial natriuretic peptide (20%). Finally, in the dorsal hypothalamic area as many as 55-75% of the neurons with spinal projections are dopaminergic, on the basis of their staining with an antiserum against tyrosine hydroxylase. These 5 neurochemically distinct projections from the hypothalamus to the spinal cord are discussed in the context of their possible functional significance.
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PMID:Neurochemical organization of the hypothalamic projection to the spinal cord in the rat. 290 38

Immunohistologic localization of tyrosine hydroxylase (TOH), dopamine-beta-hydroxylase (DBH) and selected neuropeptides (vasoactive intestinal polypeptide, gastrin-releasing peptide (GRP)/bombesin, substance P, Leu-enkephalin, Met-enkephalin, dynorphin B, neuropeptide Y (NPY), somatostatin) was used to investigate the innervation of the small bowel in a rat model of diabetic autonomic neuropathy. Paravascular mesenteric nerves (extrinsic) and intramural nerves of chronically (12-18 month) diabetic rats were characterized by the presence of numerous, markedly swollen dystrophic axons which stained intensely for TOH and DBH. The peptidergic complement of axons, however, showed no evidence of comparable dystrophic axonopathy.
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PMID:Effects of chronic experimental streptozotocin-induced diabetes on the noradrenergic and peptidergic innervation of the rat alimentary tract. 290 98

We studied five cases of central nervous system neuronal tumor, one gangliocytoma and four gangliogliomas, both ultrastructurally and immunohistochemically, using antibodies to neuroendocrine markers including tyrosine hydroxylase (TH), serotonin (5HT), somatostatin (SOM), met-enkephalin (MEK), leu-enkephalin (LEK), substance P (SP), gastrin, vasopressin, oxytocin, vasoactive intestinal polypeptide, adrenocorticotropic hormone and calcitonin. In all cases, the presence of dense-core vesicles (60-250 nm) in the neuronal elements was the characteristic ultrastructural finding. Synapses were observed in two cases. Immunohistochemically, variable numbers of neuronal cells showed positive staining for SOM in five cases, TH, MEK and LEK in three cases, and 5HT and SP in one case each. The others were negative. Positive immunoreactivity for multiple markers was shown in all cases. SOM, TH, 5HT and SP were present in the small- to medium-sized cells, while MEK and LEK were almost exclusively confined to the large cells. Our study clearly indicated that these tumors contained neuronal cells which were not homogeneous with regard to neuroendocrine markers.
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PMID:Neuroendocrine markers in central nervous system neuronal tumors (gangliocytoma and ganglioglioma). 292 88

The peptidergic innervation of parenchymal and vascular components in the human parotid gland was investigated by double-labelling fluorescence. Peptide immunoreactivity in nerve fibres was correlated with the presence of tyrosine hydroxylase (TH). By light microscopy, acinar innervation consisted of fibres with the combinations neuropeptide Y (NPY)/TH and NPY/vasoactive intestinal polypeptide (VIP). Some fibres were solely NPY, TH or VIP immunoreactive. Rarely, substance P (SP)/calcitonin gene-related (CGRP)-immunolabelled fibres were associated with acini. Intercalated ducts were often approached by NPY/TH- and VIP-containing fibres. VIP innervation of excretory ducts was sparse. Intralobular and intralobar excretory ducts, in addition to NPY and TH, revealed CGRP and CGRP/SP innervation, whereas nerve fibres on interlobar excretory ducts very rarely contained NPY and none of the other mediators. Vascular innervation consisted of NPY/TH and SP/CGRP fibres; in a few fibres SP was colocalized with leu-enkephalin. Large arteries were encircled by some VIP-positive fibres. The findings suggest a specific participation of neuropeptides and of peptide combinations in the regulation of parotid exocrine function.
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PMID:Immunocytochemical correlation of peptides and tyrosine hydroxylase in nerve fibres of the human parotid gland. 751 37

Salt-loading induces profound metabolic changes in magnocellular vasopressin (AVP)-containing neurons, including changes in levels of coexisting peptides and tyrosine hydroxylase (TH). Although many studies have been conducted on salt-loading, little information is available on the recovery processes following its cessation. In the present study, we investigated the changes in AVP, galanin (Gal), dynorphin B (Dyn-B), and TH immunoreactivities in the rat supraoptic nucleus (SON) and paraventricular nucleus (PVN) by immunocytochemistry using specific antisera against these substances. Salt-loading was induced in rats by dissolving 2% NaCl in their drinking water for 7 days. These animals were then allowed free access to fresh water for 2, 4, or 7 days prior to sacrifice. In the SON at the 7th day of salt-loading, AVP, Gal and Dyn-B immunoreactivities decreased in contrast to the marked increase in TH-immunoreactivity compared to those of control rats with free access to water. After a recovery period with free access to water, AVP and Gal immunoreactivities increased with time and returned to the control level at the 7th day. However, Dyn-B immunoreactivity did not recover even at the 7th day. Dehydration-induced TH-immunoreactive neurons almost disappeared at the 7th day. Immunoreactivities for these substances in the PVN showed a similar time course as that in the SON. These findings suggest that AVP and substances coexisting with it change with different time courses in magnocellular neurons following cessation of salt-loading.
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PMID:Rehydration process from salt-loading: recovery of vasopressin and its coexisting galanin, dynorphin and tyrosine hydroxylase immunoreactivities in the supraoptic and paraventricular nuclei. 753 8

Involvement of the IEGs in brain injury and ischemia is under intensive investigation (Gubits et al., 1993). There are several families of the IEGs. They include the fos, jun, and zinc finger genes that encode transcription factors. Products of the fos family (c-fos, fra-1, fra-2, and fos B) bind to members of the jun family (c-jun, jun B, jun D) via leucine zippers, and this dimer then binds to the AP-1 site (consensus sequence -TGACTCA-) in the promoter of target genes, which in turn regulate the expression of late response genes that produce long-term changes in cells. For example, c-fos may regulate the long-term expression of preproenkephalin, nerve growth factor, dynorphin, vasoactive intestinal polypeptide, tyrosine hydroxylase and other genes with AP-1 sites in their promoters (Curran and Morgan, 1987; Sheng and Greenberg, 1990). It is likely that the c-fos gene up-regulation observed in ischemic astrocytes leads to the changes observed in the expressions of hsp and cytoskeleton protein genes in this experimental model. This is supported by the findings of Sarid (1991) and Pennypacker et al. (1994) who have shown that AP-1 DNA binding activity in hippocampus recognized an AP-1 sequence from the promoter region of the GFAP which is a potential target gene. van de Klundert et al. (1992) also suggested the involvement of AP-1 in transcriptional regulation of vimentin. IEGs can be induced within minutes by extracellular stimuli including transmitters, peptides, and growth factors. In this study, we have shown that c-fos induction by ischemia was rapid and transient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gene expression in astrocytes during and after ischemia. 756 84

Immunohistochemical methods were used to study the developing peptidergic innervation of the human fetal prostate gland in a series of specimens ranging in gestational age from 13 to 30 wk. The overall innervation of each specimen was visualised using protein gene product 9.5 (PGP), a general nerve marker. The onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), bombesin (BOM), somatostatin (SOM), leu-enkephalin (l-ENK) and met-enkephalin (m-ENK). In addition the occurrence and distribution of presumptive noradrenergic nerves was studied using antisera to dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH). At 13 wk numerous branching PGP-immunoreactive (-IR) nerves were observed in the capsule of the developing prostate gland and surrounding the preprostatic urethra but the remainder of the gland was devoid of nerves. The majority of nerves in the capsule contained D beta H and TH and were presumed to be noradrenergic in type while other nerves (in decreasing numbers) contained NPY, l-ENK, SP and CGRP. Nerves associated with the preprostatic urethra did not contain any of the neuropeptides under investigation. At 17 wk the density of nerves in the capsule had increased and occasional m-ENK-, VIP- and BOM-IR nerve fibres were also observed. In addition PGP, D beta H-, TH-, NPY- and l-ENK-IR nerves occurred in association with smooth muscle bundles which at 17 wk were present in the outer part of the gland. Occasional PGP-IR nerves were also present at the base of the epithelium forming some of the prostatic glands. At 23 wk some of the subepithelial nerves showed immunoreactivity for NPY, VIP or l-ENK. At 26 wk smooth muscle bundles occurred throughout the gland and were richly innervated by PGP, D beta H and TH-IR nerves while a less dense plexus was formed by NPY- and l-ENK-IR nerves together with a few m-ENK-IR nerves. Occasional smooth muscle-associated varicose nerve fibres showed immunoreactivity for SP, CGRP, VIP or BOM although the majority of these types of nerve formed perivascular plexuses. Also at 26 wk numerous varicose nerve fibres were observed in association with the prostatic acini, the majority of such nerves containing NPY with a few showing immunoreactivity to VIP, l-ENK, SP or CGRP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Development of peptide-containing nerves in the human fetal prostate gland. 759 78


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