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)

We have reinvestigated the immunohistochemistry of autonomic axons supplying the guinea-pig uterine artery to determine whether non-noradrenergic paracervical ganglion neurons projecting to the artery contain immunoreactivity to dopamine-beta-hydroxylase (DBH) or somatostatin (SOM) in addition to neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). In untreated arteries no VIP axons had immunoreactivity to tyrosine hydroxylase (TH), although 9% had immunoreactivity to DBH. Somatostatin immunoreactivity was detected in 25% of non-noradrenergic axons containing NPY and VIP. After in vivo treatment with 6-hydroxydopamine (6-OHDA), noradrenergic axons containing immunoreactivity to NPY, DBH and TH were absent from the adventitia-medial junction. However, 65-70% of the non-noradrenergic axons with NPY and VIP showed DBH immunoreactivity after 6-OHDA. These axons did not show catecholamine fluorescence after incubation with pargyline together with noradrenaline, dopamine or L-DOPA. The number of axons with SOM immunoreactivity increased by 44% after 6-OHDA treatment, but only 24% of SOM axons had DBH immunoreactivity. Surgical destruction of the non-noradrenergic autonomic axons in 6-OHDA-treated animals led to the loss of all DBH immunoreactivity. These results demonstrate that DBH immunoreactivity can be detected in a small proportion of non-noradrenergic axons supplying uterine arteries from untreated animals. After chemical sympathectomy with 6-OHDA, the levels of DBH immunoreactivity in axons of non-noradrenergic neurons increased, and more axons with DBH immunoreactivity were detected. DBH immunoreactivity seemed to increase preferentially in axons with NPY and VIP, but not SOM. The number of NPY, VIP axons containing SOM also increased after 6-OHDA. These findings demonstrate that peripheral neurons containing several different potential neurotransmitters can change their levels of neuropeptides and transmitter-synthesizing enzymes in response to local environmental changes.
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PMID:Increased dopamine-beta-hydroxylase-like immunoreactivity in non-noradrenergic axons supplying the guinea-pig uterine artery after 6-hydroxydopamine treatment. 289 85

The anlages of the medial-basal hypothalamus (MBH), septopreoptic area (POA), Rathke's pouch, and the parietal cortex (CC) of rats (at 12.5, 14.5 and 16.5 days of gestation) were transplanted singly or in combination into the third ventricle of adult female rats, and the development of neurons in the grafts was investigated immunohistochemically with the use of antisera to tyrosine hydroxylase (TH), somatostatin (SRIH), ACTH, methionine enkephalin-Arg6-Gly7-Leu8 (Enk-8), rat corticotropin-releasing factor (rCRF), rat hypothalamic growth hormone-releasing factor (rhGRF), and luteinizing hormone-releasing hormone (LHRH). TH and all the peptides examined except LHRH were detected in distinct neurons in MBH grafts and in cografts of MBH plus Rathke's pouch from 12.5-day-old embryos. SRIH, rCRF, Enk-8, and TH were found in POA grafts from embryos of the same age. Although immunoreactive LHRH was first detected in neurons in POA grafts from 16.5-day-old embryos, it appeared in cografts of POA and MBH from 12.5-day-old embryos. The immunoreactive fibers developed in the grafts expressed the same characteristic behaviors as in intact brain; the fibers containing hormonal substances formed complexes with the vasculature like in the organum vasculosum laminae terminalis (OVLT) or in the median eminence, while the fibers containing neurotropic signals formed fiber networks surrounding other nerve cell bodies as if they synaptically associate. In CC grafts, the neurons contained TH, SRIH, rCRF, or Enk-8, and their axonal processes formed fiber networks. These findings suggest that all the hypothalamic neurons examined are committed by 12.5 days of gestation to develop maintaining transmitter phenotype and target recognition capacity.
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PMID:Development of hypothalamic neurons in intraventricular grafts: expression of specific transmitter phenotypes. 289 28

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 development of neuropeptide and neurotransmitter-related immunoreactivities in the rat olfactory bulb were investigated immunohistochemically by using antisera raised against substance P (SP), cholecystokinin-8 (CCK), neurotensin (NT), leucine-enkephalin or methionine-enkephalin-Arg6-Gly7-Leu8 (ENK), somatostatin (SOM), neuropeptide Y (NPY) and tyrosine hydroxylase (TH). Results obtained for the adult olfactory bulb confirmed previous observations, except for SP-like immunoreactive (SP-IR) granule cells in the main olfactory bulb (MOB) and NT-IR neurons around the modified glomerular complex (MGC) (Teicher et al., Brain Res. 194:530-535, 1980). SP-, CCK- and NT-IR neurons were observed in the MOB of the rat fetus. SP-IR neurons also appeared in the accessory olfactory bulb (AOB). Among them, NT-IR neurons in the MOB and SP-IR neurons in the AOB were observed on embryonic day 16. SP- and CCK-IR neurons in the MOB appeared on embryonic day 18. Most of these neurons were presumed to be projecting neurons. SOM-, NPY-, ENK- and TH-IR neurons appeared in the newborn rats. The number and intensity of immunostaining of these neurons continued to increase with age, producing the adult pattern, except for NT-IR neurons in the MGC and SP-IR neurons in the mitral cell layer of the AOB, which were more numerous and intensely stained in young animals.
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PMID:Neuropeptide- and neurotransmitter-related immunoreactivities in the developing rat olfactory bulb. 290 37

Activation of neurotransmitter receptors can regulate transcription in postsynaptic cells through the actions of second messengers. Trans-synaptic regulation of transcription appears to be an important mechanism controlling the synthesis of molecules involved in neuronal signaling, especially neuropeptides. Proenkephalin, vasoactive intestinal polypeptide, and somatostatin have been shown to be transcriptionally regulated by the second messenger, cyclic AMP (cAMP), as has the catecholamine synthesizing enzyme tryosine hydroxylase. cAMP-inducible elements have been mapped within these genes, and trans-acting factors which bind to several such elements have been identified. With the discovery that individual neurons generally contain multiple transmitters within their synaptic terminals, it has become important to understand in detail the mechanisms by which the synthesis of transmitters can be coregulated. Here we compare the structure and function of the proenkephalin cAMP-inducible enhancer with the mapped cAMP-inducible elements of the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and a putative cAMP-inducible element in the proto-oncogene c-fos. We have previously shown that the proenkephalin enhancer is composed of two different elements, ENKCRE-1 and ENKCRE-2. We show here that one of these, ENKCRE-2, is structurally similar to elements found within the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and binds a trans-acting factor that is competed for both in cotransfection experiments (in vivo) and in DNase I footprint assays (in vitro) by these other elements. The c-fos element has similar structural requirements to confer transcriptional induction by cAMP but competes less strongly. Protein purified by affinity chromatography with the ENKCRE-2 sequence binds to each of these elements. A second element within the proenkephalin cAMP-inducible enhancer, ENKCRE-1, binds a factor that is not competed for by these other genes and is therefore distinct. This analysis suggests a potential mechanism of transcriptional coregulation of the neuronally expressed genes investigated in this study and also demonstrates that multiple factors are involved in transcriptional activation by cAMP.
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PMID:A common trans-acting factor is involved in transcriptional regulation of neurotransmitter genes by cyclic AMP. 290 36

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

Indirect immunofluorescence histochemistry was used to study the relation among GABAergic, catecholaminergic, cholinergic, and peptidergic neurons in the rat mediobasal hypothalamus. By employing a direct double-labelling procedure using sheep antiserum against glutamic acid decarboxylase (GAD), mouse monoclonal and rabbit antibodies to neurotensin (NT) and rabbit antisera to tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), galanin (GAL), growth hormone-releasing factor (GRF), or somatostatin (SOM), it was demonstrated that GAD-positive fibers and terminals in the external part of the median eminence co-contained immunoreactivity for TH, NT, GAL or GRF, but not for SOM. In the internal part of the median eminence-infundibular stalk, GAD-positive/NT-, GAL-, and GRF-negative and GAD-positive/TH-positive fiber plexa were shown. When a recently developed direct triple-labelling procedure with biotin-conjugated mouse secondary antibodies in conjunction with diethylaminocoumarin (DAMC)-conjugated avidin was employed, presence of GAD/GAL/NT- as well as GAD/GRF/NT-containing varicosities could be demonstrated close to hypophysial portal vessels. In colchicine-pretreated animals, GAD was shown to coexist with TH, NT, or GAL in cell bodies in both the dorsomedial and ventrolateral domains of the arcuate nucleus, but with GRF only in the ventrolateral division. ChAT-positive neurons in the ventrolateral region were also TH-positive. In the ventrolateral arcuate nucleus, triple-labelling followed by elution-restaining showed GAD/NT/GAL/TH-immunoreactivities in the same cells. Similarly, double-labelling with two following elution-restaining steps showed several NT/GAL/GRF/TH-containing cell bodies in this part of the arcuate nucleus. GAD-positive cells in the anterior hypothalamic periventricular area and fibers in the pituitary neurointermediate lobe were also TH-positive. The results demonstrate complex patterns of storage of chemical messengers in neurons of the arcuate nucleus-median eminence complex. Possible neuroendocrine interactions of these systems in the control of prolactin and growth hormone secretion are discussed.
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PMID:Peptide- and transmitter-containing neurons in the mediobasal hypothalamus and their relation to GABAergic systems: possible roles in control of prolactin and growth hormone secretion. 290 36

The distribution of neurons and fibres that contain substance P, cholecystokinin-8, vasoactive intestinal polypeptide, corticotropin-releasing factor, calcitonin-gene-related peptide, choline acetyltransferase, tyrosine hydroxylase, somatostatin, leucine-enkephalin, and neuropeptide Y was examined in the parabigeminal nucleus of the rat by immunohistochemistry. Many choline acetyltransferase-like immunoreactive or calcitonin-gene-related peptide-like immunoreactive neurons were observed in the dorsal, middle and ventral subdivisions of the parabigeminal nucleus. A few corticotropin-releasing factor-like immunoreactive neurons were also seen in these three subdivisions. The double-immunostaining demonstrated that some choline acetyltransferase-like immunoreactive neurons in the dorsal and ventral subdivisions contained calcitonin-gene-related peptide. Fibres containing cholecystokinin-8, substance P or vasoactive intestinal polypeptide were abundant in the parabigeminal nucleus. Fibres containing cholecystokinin-8 were concentrated in the dorsal and ventral subdivisions, and the lateral margin of the middle subdivision, whereas many fibres containing substance P or vasoactive intestinal polypeptide existed in the lateral half of each subdivision. Fibres containing calcitonin-gene-related peptide or corticotropin-releasing factor were mostly observed around the immunoreactive neurons. Tyrosine hydroxylase-like immunoreactive fibres were scattered in the parabigeminal nucleus.
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PMID:Localization of neuroactive substances in the rat parabigeminal nucleus: an immunohistochemical study. 290 92

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

Steroid hormones modify several brain functions, at least in part by altering expression of particular genes. Of interest are those genes that are involved in cell-cell communication in the brain, for instance neuropeptide genes and genes that code for enzymes involved in synthesis of neurotransmitters. Steroid regulation of mRNA levels for several genes has been reported, including the genes coding for the neuropeptides vasopressin, corticotropin releasing factor, luteinizing hormone-releasing factor, pro-opiomelanocortin; somatostatin, preproenkephalin, and the enzyme tyrosine hydroxylase. Steroid control of releasing factor genes is consistent with classical neuroendocrine concepts of negative feedback. Steroid-induced plasticity of gene expression is sometimes in evidence, with the presence or absence of a particular steroid inducing expression of a neuropeptide gene in neurons that under other conditions do not express the gene. As a means of gaining some insight into the mechanism of action of steroid hormones, several groups have determined some of the neuropeptide profiles of neurons that contain receptors for steroid hormones. Marked heterogeneity is found, in that often only a subpopulation of phenotypically-similar neurons, even within a single brain area, contains receptors for a given steroid.
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PMID:Regulation of neuropeptide gene expression by steroid hormones. 307 66


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