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)

Nitric oxide synthase immunoreactivity was detected in neurons and fibers of the rat pontine medulla. In the medulla, nitric oxide synthase-positive neurons and processes were observed in the gracile nucleus, spinal trigeminal nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus, nucleus ambiguus, medial longitudinal fasciculus, reticular nuclei and lateral to the pyramidal tract. In the pons, intensely labeled neurons were observed in the pedunculopontine tegmental nucleus, paralemniscal nucleus, ventral tegmental nucleus, laterodorsal tegmental nucleus, and lateral and medial parabrachial nuclei. Labeled neurons and fibers were seen in the interpeduncular nuclei, dorsal and median raphe nuclei, central gray and dorsal central gray, and superior and inferior colliculi. Double-labeling techniques showed that a small population (< 5%) of nitric oxide synthase-positive neurons in the medulla also contained immunoreactivity to the aminergic neuron marker tyrosine hydroxylase. The majority of nitric oxide synthase-immunoreactive neurons in the dorsal and median raphe nuclei were 5-hydroxytryptamine-positive, whereas very few 5-hydroxytryptamine-positive cells in the caudal raphe nuclei were nitric oxide synthase-positive. Virtually all nitric oxide synthase-positive neurons in the pedunculopontine and laterodorsal tegmental nuclei were also choline acetyltransferase-positive, whereas nitric oxide synthase immunoreactivity was either low or not detected in choline acetyltransferase-positive neurons in the medulla. The results indicate a rostrocaudal gradient in the intensity of nitric oxide synthase immunoreactivity, i.e. it is highest in neurons of the tegmentum nuclei and neurons in the medulla are less intensely labeled. The majority of cholinergic and serotonergic neurons in the pons are nitric oxide synthase-positive, whereas the immunoreactivity was either too low to be detected or absent in the large majority of serotonergic, aminergic and cholinergic neurons in the medulla.
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PMID:Nitric oxide synthase immunoreactivity in rat pontine medullary neurons. 751 1

Microinfusion of serotonin (5-hydroxytryptamine; 5-HT) into the ventral tegmental area enhances the release of dopamine in the nucleus accumbens, a major target of midbrain dopamine neurons. We examined the synaptic basis for 5-HT modulation of neurons in the ventral tegmental area which either (i) project to the nucleus accumbens or (ii) contain the catecholamine synthesizing enzyme tyrosine hydroxylase, a marker of dopamine neurons in this brain region. In the first study, immunoperoxidase labeling of 5-HT in the ventral tegmental area was combined with retrograde transport of gold particles following unilateral injections of the tracer into the nucleus accumbens of adult rats. The gold particles had been previously coupled to wheat germ agglutinin conjugated to inactive horseradish peroxidase. Gold particles were enlarged for visualization using a silver enhancement procedure. By brightfield microscopy, retrogradely labeled neurons contained black punctate granules within their perikarya and proximal processes. The labeled cells were scattered ipsilateral to the injection within the paranigral and parabrachial subdivisions of the ventral tegmental area. Both regions also contained 5-HT immunoreactive varicosities. By electron microscopy, irrespective of the ventral tegmental subdivision, 5-HT labeling was seen primarily in unmyelinated axons and axon terminals. The terminals contained small, clear and large dense core vesicles and ranged from 0.3 micron to 1.4 microns in cross-sectional diameter. 22% (n = 250) of the axon terminals containing 5-HT immunoreactivity formed synaptic contacts with neurons containing the retrograde label. Of these 5-HT terminals, 16% formed asymmetric type contacts and 6% formed symmetric junctions on the retrogradely labeled neurons. The remaining 5-HT terminals were either apposed to (but lacked recognized synapses on) perikarya and large dendrites containing the retrogradely transported protein-gold tracer or contacted unlabeled neurons. In the second set of experiments combining immunoperoxidase of 5-HT and immunogold silver for tyrosine hydroxylase, 32% (n = 250) of the 5-HT-labeled terminals formed synaptic junctions with perikarya or dendrites containing tyrosine hydroxylase immunoreactivity. Of these 5-HT terminals, 23% formed asymmetric type junctions. The remainder were either symmetric or lacked recognized membrane densities. The prominence of asymmetric junctions formed by 5-HT-labeled terminals on neurons projecting to the nucleus accumbens and those containing tyrosine hydroxylase in the ventral tegmental area suggests a cellular basis for serotonergic excitation of mesoaccumbens dopamine neurons. Additionally, the multiplicity of junctions formed by 5-HT terminals on targets with or without retrograde labeling or tyrosine hydroxylase immunoreactivity is consistent with known diverse physiological actions of 5-HT in the tegmental area.
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PMID:Synaptic structure and connectivity of serotonin terminals in the ventral tegmental area: potential sites for modulation of mesolimbic dopamine neurons. 752 22

Although the general organization of the sheep brain is similar to that of other mammals, there are species differences in the fine architecture and neurotransmitter distribution. In sheep, perikarya are generally scattered, unlike the situation in rodents where they are clustered. The same organization is observed in cows and primates. The density of neurones immunoreactive for tyrosine hydroxylase in the dorsorostral diencephalon of sheep is lower than in rodents; A14 and A15 dopaminergic cell groups do not present a dorsal part. Only one adrenergic group, C2, is observed in the dorsomedial medulla oblongata. GnRH-immunoreactive neurones are mainly found in the anterior hypothalamic-preoptic areas, a few being present in the mediobasal hypothalamus. The density of several neurones containing neuropeptides (for example vasoactive intestinal polypeptide, cholecystokinin and somatostatin) in the caudal brain of sheep is lower than in other species and in the forebrain of sheep. These differences contribute to different patterns of innervation of brain areas compared with other species. For example, the suprachiasmatic nucleus does not present a dense network of fibres immunoreactive for 5-hydroxytryptamine and neuropeptide Y as observed in rats. These morphological studies constitute information necessary for further physiological investigations.
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PMID:Distribution of neurotransmitters in the sheep brain. 762 14

Annual variations in the secretion of LH are responsible for seasonal changes in ovulatory activity in ewes. This hormonal pattern reflects an increase in the intensity of the negative feedback exerted by oestradiol under long days. Neuropharmacological studies have shown that this inhibition of LH secretion involves activation of catecholaminergic systems from preoptic and mediobasal hypothalamus (MBH) by oestradiol during anoestrus, and that 5-hydroxytryptamine inputs may also play a role. Within the MBH, the most important structures appear to be the retrochiasmatic region of the hypothalamus, which contains the A15 dopaminergic nucleus, and the median eminence, which contains the axon terminals of the GnRH cells controlling the pulsatile release of LH. In ovariectomized ewes in which oestradiol tonically inhibits LH secretion during the anoestrous season, LH pulse frequency is increased when the cells of the A15 nucleus are destroyed. The median eminence and other mediobasal structures contain more catecholamines and their metabolites under long days than under short days. Microdialysis of the A15 nucleus in vivo during long days revealed increased catecholaminergic activity under oestradiol treatment due to stimulation of tyrosine hydroxylase, the rate-limiting enzyme in the pathway of catecholaminergic synthesis. Tyrosine hydroxylase activity within the median eminence is increased under the various photoperiodic regimens that inhibit LH secretion. Neurochemical changes in the A15 nucleus and median eminence, in response to photoperiodic or oestradiol treatments, suggest a functional relationship which acts at the level of the GnRH axon terminals.
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PMID:Dopaminergic control of LH secretion by the A15 nucleus in anoestrous ewes. 762 20

The development of dystrophic cardiac muscle is related to increases in sympathetic nervous system activity but little is known regarding possible central neural mechanisms that may be involved in cardiomyopathy. The inbred cardiomyopathic hamster is an animal model for studying the development and mechanisms of necrosis in cardiac muscle which resemble non-vascular myocardial diseases of man. Because monoamines are known to play a major role in central regulation of the cardiovascular system, we compared the distribution and density of tyrosine hydroxylase (TH) and 5-hydroxytryptamine (5-HT) immunostaining in the brains of cardiomyopathic hamsters (strain CHF-146), a related strain (CHF-148) of non-cardiomyopathic albino hamsters, and golden Syrian hamsters for possible differences in neurochemical organization. At the time of sacrifice, the cardiomyopathic hamsters exhibit small, calcified lesions on the surface of the ventricular cardiac muscle (early necrotic phase). Brain sections from each group were processed identically and simultaneously. The results show that there were significant differences among strains in the parabrachial nucleus with respect to the two neurochemicals examined. In golden Syrian and albino hamsters, TH and 5-HT immunoreactive axons were lightly-to-moderately stained in the lateral parabrachial nucleus. In the cardiomyopathic hamster, there were significantly more densely stained TH and 5-HT immunoreactive axons in the lateral parabrachial nucleus, in particular the inner part of the external lateral subnucleus. Because the lateral parabrachial nucleus, including the external lateral subnucleus, is known to be involved in regulation of the cardiovascular system, the differential distribution of TH and 5-HT in the parabrachial nucleus of cardiomyopathic hamsters in comparison to normal hamsters suggests that the parabrachial nucleus could be involved in sympathetic mechanisms related to the development of necrosis in cardiac muscle of the cardiomyopathic hamster.
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PMID:Monoamines in the parabrachial nucleus of the cardiomyopathic hamster. 766 67

A major input to the substantia nigra is from the 5-hydroxytryptamine-containing neurons in the dorsal raphe nucleus. In order to examine the morphology and distribution of this projection, rats were given injections of the anterograde tracers, Phaseolus vulgaris-leucoagglutinin or biocytin, in the dorsal raphe nucleus and the substantia nigra was examined at both the light and electron microscopic levels. In addition, sections of the substantia nigra were immunostained for 5-hydroxytryptamine and examined in both the light and electron microscopes. Since dopaminergic neurons of the substantia nigra are known to be responsive to stimulation of the raphe and to applied 5-hydroxytryptamine, sections that contained anterogradely labelled terminals were further processed to reveal tyrosine hydroxylase immunoreactivity to determine whether the raphe input makes direct synaptic contact with dopaminergic neurons. Light microscopic analysis revealed that all divisions of the substantia nigra received input from the dorsal raphe which, in agreement with previous observations, showed a topographical organization. In that formed asymmetrical synaptic contact with dendritic shafts and spines. The synaptic boutons were often associated with subjunctional dense bodies. Terminals that displayed immunoreactivity for 5-hydroxytryptamine had a similar morphology, synaptic specialisations and postsynaptic targets to the anterogradely labelled terminals. In those sections that were stained for both anterogradely labelled terminals and tyrosine hydroxylase, the raphe-nigral terminals were seen to form asymmetrical synaptic contact with the dendrites of the dopaminergic neurons. It is concluded that dendrites of dopaminergic neurons in the substantia nigra pars reticulata represent at least one of the synaptic targets of the raphe-nigral projection and that these contacts provide an anatomical substrate for the effects of the dorsal raphe, and presumably 5-hydroxytryptamine, on dopaminergic systems in the substantia nigra.
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PMID:Ultrastructure and synaptic targets of the raphe-nigral projection in the rat. 769 Sep 10

Although the general patterns of the developing histaminergic system in the rat brain are known, no comparative studies between the development of the brain histaminergic system and the development of other neuroactive substances have yet been published. Interestingly, separate immunohistochemical studies on the development of the 5-HT system and on the catecholaminergic system in the rat imply common features in the different aminergic systems. Therefore, the spatial distribution of histamine-immunoreactive (HA-ir) neurons and nerve fibers was compared to the distribution of 5-hydroxytryptamine (5-HT)-, and tyrosine hydroxylase-immunoreactive (TH-ir) ones in the developing rat brain between embryonic days 12 (E12) and 20 (E20) by using a double-immunostaining method. The high-pressure liquid chromatography (HPLC) fluorometric method was used for determination of histamine concentration in different brain regions during the same period of development and synthetic oligonucleotide probes complementary to the rat histidine decarboxylase (HDC) to determine the origin of HA in the brain during the development with in situ hybridization. The immunohistochemical results revealed co-localization of HA and 5-HT within a subgroup of cells in the developing raphe nuclei between E14 and E18. From E18 onwards HA immunoreactivity started to gradually disappear from the rhombencephalon, and was totally abolished by E20, while 5-HT-ir cells continued to establish their adult positions. No significant colocalization of HA and TH immunoreactivities was detected. The biochemical results were in agreement with the immunohistochemical ones and confirmed that histamine detected in the early developing brain is authentic. A positive in situ hybridization signal for HDC was detected in a small area in the ventrolateral pons in the same areas as HA- and HDC-ir cell bodies at E16, suggesting that at least some HA may be synthesized locally. These results confirm that HA is one of the first neurotransmitters to appear in the developing brain. In addition, the transient co-localization of HA and 5-HT immunoreactivities and the transient HDC expression at E16 within the developing pontine raphe nuclei may imply an interesting and a more general role for HA in modification of brain development.
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PMID:Distribution of histamine-, 5-hydroxytryptamine-, and tyrosine hydroxylase-immunoreactive neurons and nerve fibers in developing rat brain. 779 75

Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous electrophysiological studies have demonstrated that cells of the caudal SN and the VTA have similar characteristics, whereas cells in the rostral SN have distinctly different properties. In the present study, we confirmed that each region has tyrosine hydroxylase-positive neurons and determined, using high-performance liquid chromatography, that DA levels were similar in rostral and caudal SN, but lower in SN than in VTA. In each region, application of veratrine, which was shown by intracellular recordings to have a reversible depolarising action, evoked a signal attributable to DA and distinguishable from that of 5-HT. Release signals were monitored every 250 ms with a spatial resolution of less than 50 microns.l DA release was calcium-dependent and was not detectable in a catecholamine-poor area such as the cerebellum, or in mid-brain tissue pre-treated with reserpine. Within the normal mid-brain, the amount of DA released was correlated with tissue content in that it was higher in the VTA than in either region of SN. It is concluded that DA released from somato-dendritic parts of mid-brain neurons exhibits site-specific variation. This is the first report of direct monitoring of DA and 5-HT release from these regions with in situ electrodes and demonstrates the utility of fast-scan cyclic voltammetry to investigate the mechanisms and possible non-classical functions of somato-dendritic DA release.
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PMID:Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral tegmental area in vitro. 781 78

The biosynthesis of catecholamines and indoleamines was investigated in the sea pansy Renilla koellikeri by radiochemical screening of tissue samples exposed in vivo to labelled amino acid precursors and analysed by high-performance liquid chromatography coupled with electrochemical detection. Incubation of sea pansy tissues in [3H]tyrosine resulted in substantial accumulation of radioactivity recovered in chromatograms coeluting with tyrosine and 4-hydroxy-3-methoxy mandelic acid and, to a lesser extent, with 3,4-dihydroxy-phenylalanine, dopamine, norepinephrine, epinephrine, normetanephrine and 3,4-dihydroxyphenyl acetic acid. The catecholamine synthesis inhibitor alpha-methyl-p-tyrosine effectively reduced several of these [3H]tyrosine by-products formed as well as endogenous stores of these amines. Incubations in [3H]tryptophan resulted in large amounts of radioactivity associated with liquid chromatographic peaks coeluting with tryptophan and 5-hydroxytryptophan and lesser amounts with 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine and 5-hydroxy-3-indole acetic acid. The indoleamine synthesis inhibitor p-chlorophenylalanine reduced the amounts of products formed and depleted stores of the endogenous indoleamines. Enzyme activities which appear to involve tyrosine hydroxylase (EC 1. 12. 16. 2), tryptophan hydroxylase (EC 1. 14. 16. 4) and phenylethanolamine N-methyltransferase (EC 2. 1. 1. 28) were also detected in rachidial tissues by HPLC analysis of reaction products (hydroxylases) and by a radioenzymatic assay (methyltransferase). The sea pansy being a representative of the earliest invertebrates possessing a nervous system, these results support the hypothesis that vertebrate-like enzymatic pathways for the biosynthesis and degradation of monoamine neurotransmitters were conserved throughout evolution.
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PMID:Evidence for biosynthesis and catabolism of monoamines in the sea pansy Renilla koellikeri (Cnidaria). 784 75

The autonomic nervous system of mammals displays extensive neurotransmitter diversity. The guinea-pig sympathetic nervous system has served as a model for in vivo studies of neurotransmitter co-expression. We have developed methods for the dissociation and long-term culture of adult guinea-pig prevertebral sympathetic ganglia. The neurotransmitter properties of cultured adult guinea-pig sympathetic neurons from the celiac and superior mesenteric ganglia were examined. Cultured principal neurons were found to display many of their in vivo neurotransmitter characteristics, including catecholamine-specific histofluorescence and immunoreactivity for tyrosine hydroxylase and the neuropeptides, neuropeptide Y, somatostatin and vasoactive intestinal polypeptide. In addition, the cultures of both ganglia displayed the various neurotransmitter characteristics in approximately the same percentage of the cultured neurons as reported in in vivo studies. A small percentage of principal neurons and many small, intensely fluorescent-like cells labeled with antibodies against 5-hydroxytryptamine. Many of the principal neurons were found to bear 5-hydroxytryptamine3 receptors, suggesting a possible role for this neurotransmitter in neuron-neuron and small, intensely fluorescent cell-neuron transmission. We conclude that adult guinea-pig sympathetic neurons retain their neurotransmitter phenotypes when grown in dissociated cell culture. These properties include the co-expression of the classical transmitters, norepinephrine, 5-hydroxytryptamine and neuropeptides. This culture preparation will prove to be valuable in future studies on the functional properties of these neurons and their development.
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PMID:Neurotransmitter properties of guinea-pig sympathetic neurons grown in dissociated cell culture--I. Adult neurons. 790 16


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