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)

Peripherally administered gamma-aminobutyric acid (GABA) alters cardiovascular function and has been reported to enhance ouabain-induced cardiotoxicity in vivo. Control and reserpinized rat hearts were perfused in vitro to determine if GABA directly evokes bradycardia by GABAA receptors, interacts with ouabain, and if noradrenergic mechanisms are required. Also, double-staining immunohistochemistry was employed to determine whether GABA-ergic and noradrenergic synthetic enzymes were juxtaposed within atrial tissue. The main results were as follows. GABA produced a dose-dependent bradycardia (p < 0.05) by stimulating GABAA receptors in Langendorff-perfused hearts. Reserpinized hearts were unresponsive (p < 0.05) to GABA, except at the highest dose (20 mg/ml). Ouabain-induced cardiotoxicity was enhanced (p < 0.05) by GABA in isolated control, but not reserpinized hearts. Lastly, glutamic acid decarboxylase and tyrosine hydroxylase immunoreactivities were in close proximity in atrial slices. Collectively, the results document that GABA causes bradycardia and enhances ouabain cardiotoxicity by modulating noradrenergic mechanisms in the isolated rat heart. Since the synthetic enzymes for GABA and norepinephrine were in close proximity in atrial tissue, these transmitters may interact under physiological conditions.
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PMID:Cardiac noradrenergic mechanisms mediate GABA-enhanced ouabain cardiotoxicity. 787 72

Treatment of P19 embryonal carcinoma cells with retinoic acid induces their differentiation into a population of cells consisting of neurons and other cell types normally derived from neuroectoderm. We used immunohistological and histochemical techniques to identify some of the neurotransmitters in the P19-derived neurons. The majority of neurons contained GABA, glutamic acid decarboxylase, and GABA-transaminase. Neuropeptide Y and somatostatin were less frequently found and both were partially co-expressed with GABA and with one another. Smaller numbers of cells were positive for tyrosine hydroxylase, DOPA decarboxylase, serotonin, calcitonin gene-related peptide, galanin and substance P. The variety and proportions of cells with different transmitter types were reproducible from one experiment to the next and varied very little over 40 days in culture except for cells containing enkephalin, which were abundant only in mature cultures of 32 days or more. Synapses formed between neurons and some contained both small clear and large dense-core vesicles within the presynaptic bouton. Because GABA, neuropeptide Y and somatostatin are abundant in P19-derived neurons as well as in embryonic neurons in rostral regions of the mammalian CNS, we suggest that the developmental events occurring in P19 cell cultures closely resemble those of the embryonic neuroectoderm.
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PMID:Neurons derived from P19 embryonal carcinoma cells have varied morphologies and neurotransmitters. 791 Jun 70

The aim of this study was to characterize further the transmitter content and the location of the parent cells of tyrosine hydroxylase-immunoreactive boutons terminating on luteinizing hormone-releasing hormone- and glutamic acid decarboxylase-immunoreactive neurons in the rat medial preoptic area. Electron microscopic immunostaining for luteinizing hormone-releasing hormone, tyrosine hydroxylase or glutamic acid decarboxylase was performed on desipramine-pretreated (to protect norepinephrine and epinephrine axons) rats which received a stereotaxic injection of 6-hydroxydopamine into the medial preoptic area anteroventral periventricular nucleus 48 h prior to sacrifice. This treatment induced acute degeneration of dopamine axon terminals characterized by the development of autophagous cytolysosomes, an early morphological sign of catecholamine axon degeneration. To further define the cells of origin of these dopamine boutons, the anterograde marker Phaseolus vulgaris leucoagglutinin was iontophoretically applied to the zona incerta. Six days later, rats received a 6-hydroxydopamine injection into the zona incerta or the lateral ventricle, and 48 h later, double immunostaining was performed for Phaseolus vulgaris leucoagglutinin and tyrosine hydroxylase, luteinizing hormone-releasing hormone, or glutamic acid decarboxylase on preoptic area vibratome sections. Following the 6-hydroxydopamine injection into the anteroventral periventricular nucleus, autophagous cytolysosome-containing degenerated axons were found in synaptic contact with both luteinizing hormone-releasing hormone and GABA neurons in the medial preoptic area, confirming that these are dopaminergic connections. Following the double injection treatment, 6-hydroxydopamine-induced degenerated, Phaseolus vulgaris leucoagglutinin-labeled dopamine axons originating in the zona incerta were not found to contact luteinizing hormone-releasing hormone-containing or GABA cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luteinizing hormone-releasing hormone and gamma-aminobutyric acid neurons in the medial preoptic area are synaptic targets of dopamine axons originating in anterior periventricular areas. 809 41

The regeneration of islet cells in a transgenic mouse strain harboring the interferon-gamma gene (IFN-gamma) linked to the insulin promoter DNA fragment (ins-IFN-gamma) is described. The regeneration follows the loss of islets by an immune response provoked by IFN-gamma and manifests in the proliferation of duct cells, the presence of progenitor cells, and the formation of buds and isletlike structure. All three types (A, B, and D) of four endocrine cells identified by immunolabeling are present. The progenitor cells express neuronal enzymes, tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD), as revealed by specific antibodies. The results indicate that the islet regeneration closely resembles the embryonic islet differentiation and serves as a model for studying islet development. The expression of neuronal enzymes by islet progenitor cells signifies yet unknown relationships to the nervous tissue. GAD, recognized as an autoantigen in insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome, may provide a clue to the mechanism of autoimmune disease.
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PMID:A transgenic model for studying islet development. 814 22

The neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5) were compared for their effects in promoting the survival and/or regulation of expression of phenotypic markers of dopaminergic and GABAergic neurons in cultures derived from embryonic rat ventral mesencephalon. Dopaminergic neuron number and phenotypic expression were monitored by tyrosine hydroxylase (TH) immunocytochemistry, and measurement of high-affinity dopamine uptake activity and dopamine content, respectively. High-affinity GABA uptake, glutamic acid decarboxylase (GAD) activity, and endogenous GABA content were used to detect GABAergic neurons. Seven days of treatment with either BDNF or NT-3 resulted in dose-dependent increases in the number of TH-positive neurons, with maximal responses of 3-fold and 2.3-fold, respectively. Dopamine uptake activity and dopamine content were similarly increased. The effects of BDNF and NT-3 on dopamine uptake activity showed no additivity. NT-4/5 treatment elicited the greatest increase (7-fold) in the number of TH-positive neurons, as well as a 2.6-fold increase in dopamine content. In marked contrast to BDNF or NT-3, NT-4/5 had no effect on dopamine uptake capacity. BDNF, NT-3, or NT-4/5 also produced dose-dependent elevations of 2-3-fold in GABA uptake activity. These effects were not additive. GAD activity was increased by BDNF (1.8-fold) and NT-3 (threefold) treatment, but not by NT-4/5, whereas GABA content was increased to a similar extent by all three neurotrophins. NGF had no effect on any of the parameters measured in this study. Northern analyses indicated that the mRNAs encoding TrkB and TrkC, the functional high-affinity receptors for BDNF and NT-4/5, and NT-3, respectively, are expressed in the substantia nigra of adult rat brain, as well as in cultures of developing ventral mesencephalon. Taken together, our results indicate that BDNF and NT-3 have broadly similar effects in promoting the survival and differentiated phenotype of both dopaminergic and GABAergic neurons of the developing substantia nigra. Although BDNF and NT-4/5 are thought to act through the same high-affinity receptor, TrkB, it is evident that these two neurotrophins have distinct as well as overlapping actions toward mesencephalic dopaminergic or GABAergic neurons.
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PMID:Overlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT-4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. 828 41

To determine if systemically administered antibodies could reach antigenic targets and cause immunologic lesions in brains of newborn rats, murine monoclonal antibodies against rat acetylcholinesterase were injected i.p. on the first postnatal day. As early as 24 h after injection, antibodies were detected immunocytochemically in brain parenchyma, along with punctate debris that showed intense cholinesterase activity. Total acetylcholinesterase activity in the brain dropped by 30%, and 10S activity was almost undetectable at day 3, implying true enzyme loss since the antibodies did not directly impair catalytic function. At day 7, 10S acetylcholinesterase began to recover but the activity remained only half that of controls. At day 12, total acetylcholinesterase activity was still reduced (30% in whole brain, 40% in cerebral cortex), consistent with lasting damage to cholinesterase-expressing cortical neurons. This conclusion was confirmed by histochemical experiments showing a nearly complete disappearance of acetylcholinesterase fiber-staining in cerebral cortex and basal ganglia at days 4 and 8, with residual deficits at day 12. Choline acetyltransferase activity decreased in the cerebral cortex, implying a loss of cholinergic terminals, but specifically immunoreactive perikarya remained abundant in the basal forebrain. Immunocytochemistry showed no obvious changes in three non-cholinergic markers: tyrosine hydroxylase, tryptophan hydroxylase, and glutamic acid decarboxylase. Overall, it appeared that acetylcholinesterase antibodies induced widespread but reversible damage of cholinergic fibers and terminals, while sparing cholinergic cell bodies and many other neural systems.
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PMID:Lesion of central cholinergic systems by systemically administered acetylcholinesterase antibodies in newborn rats. 851 43

The present study was undertaken to determine the frequency and distribution of GABAergic neurons within the rat pontomesencephalic tegmentum and the relationship of GABAergic cells to cholinergic and other tegmental neurons projecting to the hypothalamus. In sections immunostained for glutamic acid decarboxylase (GAD), large numbers of small GAD-positive neurons (approximately 50,000 cells) were distributed through the tegmentum and associated with a high density of GAD-positive varicosities surrounding both GAD-positive and GAD-negative cells. Through the reticular formation, ventral tegmentum, raphe nuclei, and dorsal tegmentum, GAD-positive cells were codistributed with larger cells, which included neurons immunostained on adjacent sections for glutamate, tyrosine hydroxylase (TH), serotonin, or choline acetyltransferase (ChAT). In sections dual-immunostained for GAD and ChAT, GABAergic neurons were seen to be intermingled with less numerous cholinergic cells (approximately 2,600 GAD+ to approximately 1,400 ChAT+ cells in the laterodorsal tegmental nucleus, LDTg). Retrograde transport of cholera toxin (CT) was examined from the posterior lateral hypothalamus, where a major population of cortically projecting neurons are located. A small number of GABAergic cells were retrogradely labeled, representing a small percentage of all the GABAergic neurons (approximately 1%) and of all the hypothalamically projecting neurons (approximately 6%) in the tegmentum. The double-labeled GAD+/CT+ cells were commonly found ipsilaterally within 1) the deep mesencephalic reticular field, codistributed with putative glutamatergic projection neurons; 2) the ventral tegmental area, substantia nigra compacta, and retrorubral field, codistributed with dopaminergic projection neurons; 3) dorsal raphe, codistributed with serotonergic projection neurons; and 4) laterodorsal and pedunculopontine tegmental nuclei, codistributed with and in similar proportion to cholinergic projection cells (20-30% in LDTg). Acting as both projection and local neurons, the pontomesencephalic GABAergic cells would have the capacity to modulate the influence of the "ascending reticular activating system" and its chemically specific constituents upon cortical activation.
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PMID:GABAergic neurons in the rat pontomesencephalic tegmentum: codistribution with cholinergic and other tegmental neurons projecting to the posterior lateral hypothalamus. 864 69

Neurons in very low density hippocampal cultures that are physiologically identified as either GABAergic inhibitory or glutamatergic excitatory all contain mRNA for the gamma-aminobutyric acid (GABA) synthetic enzyme, glutamic acid decarboxylase (GAD), as detected by single cell mRNA amplification and PCR. However, consistent with the physiology, immunocytochemistry revealed that only a subset of the neurons stain for either GAD protein or GABA. A similar fraction hybridize with RNA probes for GAD65 and GAD67. Hippocampal CA1 pyramidal neurons in slice preparations, which are traditionally thought to be excitatory, also contain mRNA for GAD65 and GAD67. Hippocampal neurons in culture did not contain mRNA for two other neurotransmitter synthesizing enzymes, tyrosine hydroxylase, and choline acetyl transferase. These data suggest that in some neurons, presumably the excitatory neurons, GAD mRNA is selectively regulated at the level of translation. We propose that neurotransmitter phenotype may be posttranscriptionally regulated and neurons may exhibit transient phenotypic plasticity in response to environmental influences.
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PMID:Presence of mRNA for glutamic acid decarboxylase in both excitatory and inhibitory neurons. 879 Apr 19

We have previously shown that dopamine differentiation factors (DDF) can stimulate the novel expression of tyrosine hydroxylase (TH) in the phenotypically plastic neurons of the embryonic mouse striatum (Du et al., J. Neurosci., 14 (1994) 7688-7694; Du and Iacovitti, J. Neurosci., 15 (1995) 5420-5427). The present study sought to determine whether TH induction required down-regulation of an existing GABAergic trait in striatal neurons or whether enzymes of both neurotransmitter systems were simultaneously expressed. Immunocytochemical analysis revealed that, following treatment with DDFs, TH and the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) were co-expressed in the same neurons. Moreover, GAD enzyme activity was not affected by the dramatic increase in TH. Thus, the induction of a novel neurotransmitter phenotype in brain neurons does not appear to occur at the expense of the existing phenotype.
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PMID:Co-expression of tyrosine hydroxylase and glutamic acid decarboxylase in dopamine differentiation factor-treated striatal neurons in culture. 882 86

This study was aimed at showing the distribution and projection of the medullary cardiovascular control neurons that contain a standard neurotransmitter or a related enzyme in the rat. A small amount of HRP was injected into either the depressor area of the caudal ventrolateral medulla (D-CVLM) or the pressor area of the rostral ventrolateral medulla (P-RVLM). Using an immunohistochemical method, we identified HRP-labelled neurons which were stained with antiserum to glutamate (Glu), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) or phenylethanolamine N-methyltransferase (PNMT). Our findings are summarized as follows. (1) The Glu-containing neurons in the nucleus tractus solitararii (NTS) project to the D-CVLM (n = 279, 100% assumed as a standard value) and P-RVLM (n = 225, 81% against the standard), indicating divergent excitatory projection. (2) The GAD-containing neurons in the NTS (n = 74, 27% against the standard) project to the P-RVLM, indicating the convergent inhibitory projection. (3) The projections of the TH-containing neurons from the NTS (n = 19, 7% against the standard) and CVLM (n = 4, 1% against the standard) to the P-RVLM are weaker than those of the GAD-containing neurons, suggesting that the catecholaminergic neurons play a minor role in inhibition of the sympathetic activity of the P-RVLM neurons. These results suggest that the glutamatergic NTS neurons excite both the P-RVLM and D-CVLM neurons, and the gamma-aminobutyric acid (GABA)ergic NTS and CVLM neurons inhibit the sympathetic activity of the P-RVLM neurons.
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PMID:Distribution and projection of the medullary cardiovascular control neurons containing glutamate, glutamic acid decarboxylase, tyrosine hydroxylase and phenylethanolamine N-methyltransferase in rats. 908 94


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