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 effect of lesions of the catecholamine nerve terminals in the medial prefrontal cortex of the rat on neurotransmitter mechanisms within the basal ganglia has been investigated. Bilateral 6-hydroxydopamine lesions were stereotaxically placed in the dopamine-rich (DA) area of th frontal cortex. Animals were pretreated with desmethylimipramine to block the uptake of neurotoxin into noradrenergic (NA) terminals and to make it more selective for DA terminals. The lesion produced a selective reduction of both NA and DA from the medial prefrontal cortex, a result related to falls in tyrosine hydroxylase activity at this site. Lesioned animals showed enhanced DA turnover and utilisation in striatal and limbic regions. There was no change in subcortical tyrosine hydroxylase activity. In addition there were significant falls in other putative neurotransmitters within basal sites, including 5-hydroxytryptamine and GABA. Decreased activity of the neurotransmitter-synthesizing enzyme glutamate decarboxylase and choline acetyltransferase was also recorded in certain regions of the basal ganglia. The results suggest that frontal cortical catecholamine systems may serve to regulate various neurotransmitter mechanisms in the basal ganglia.
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PMID:Effect of 6-hydroxydopamine lesions of the medial prefrontal cortex on neurotransmitter systems in subcortical sites in the rat. 616 Dec 14

Peptide, 5-hydroxytryptamine (5-HT)-, tyrosine hydroxylase (TOH)-, and glial fibrillary acidic protein (GFAP)-like immunoreactivity was studied in the optic tectum of Rana pipiens. Peroxidase-antiperoxidase and indirect immunofluorescence single- and double-labeling methods were used to compare differential laminar distribution of each of these substances. Substance P (SP), leucine-enkephalin (LENK), cholecystokinin octapeptide (CCK8), bombesin (BOM), avian pancreatic polypeptide (APP), and possibly neurotensin display unique individual patterns of laminar distribution of processes and cell bodies throughout the tectum. A correlative analysis of the topographical distribution of SP, LENK, BOM, and APP on the basis of double-labeled sections shows a precise laminar segregation of these substances. Vasoactive intestinal peptide-, beta-endorphin-, and ranatensinlike immunoreactivity is consistently absent from our material. 5HT- and TOH-like immunoreactivity discloses a reticular array of fibers without clear evidence of laminar organization. This peptide-like laminar organization is particularly elaborate throughout the superficial neuropil of the optic tectum, the major retinorecipient zone. The pattern of lamination demonstrated in the present study differs in several important features from that previously described on the basis of several histological methods. The cells of origin of processes (axons and/or dendrites) in the superficial tectal neuropil may be either intrinsic or extrinsic to the tectum. Special reference is made to conflicting evidence regarding the possibility of a retinal contribution to peptide-like tectal lamination.
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PMID:Laminar organization of peptide-like immunoreactivity in the anuran optic tectum. 619 80

Immunocytochemical methods were used to define the distribution of enkephalin (ENK), substance P (SP), tyrosine hydroxylase (TH), and serotonin (5-hydroxytryptamine: 5HT) in the rat septum. A dense plexus of axons containing enkephalin-like immunoreactivity is found in the intermediate lateral septal nucleus. This is surrounded laterally by SP-containing cell bodies and axons and medially by ENK-containing cell bodies. Both SP- and ENK-immunoreactive axons form pericellular and peridendritic terminal arbors around lateral septal neurons. TH-positive axons are distributed throughout the septum and form dense pericellular terminal baskets around scattered neurons in the medial half of the intermediate lateral septal nucleus and in the extreme lateral septum. Very few SP and TH immunoreactive axons are present in the ENK immunoreactive plexus zone. 5HT-immunoreactive axons are most dense at the lateral edge of the ventral and intermediate lateral septal nuclei but form pericellular terminal arbors only in the dorsal lateral septal nucleus, in the septofimbrial nucleus, and in the dorsal cap of the medial septal nucleus. These results indicate that the dorsal and intermediate lateral septal nuclei include three histochemically distinct laminated subfields: (1) an ENK immunoreactive axonal plexus within the lateral aspect of the intermediate lateral septal nucleus, (2) a more medial region of scattered ENK immunoreactive perikarya and similarly scattered TH immunoreactive pericellular baskets, and (3) a dorsolateral zone occupied by SP neurons and 5HT-containing pericellular baskets. Thus, the data suggest that SP- and ENK-containing neuronal populations in the lateral septum receive different monoaminergic inputs. Further, the somewhat exclusive laminated pericellular termination of peptide- and catecholamine-containing axons in the lateral septum predicts very different functional and pharmacological properties among zones.
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PMID:Distribution of enkephalin, substance P, tyrosine hydroxylase, and 5-hydroxytryptamine immunoreactivity in the septal region of the rat. 620 28

Regional effects of DSP 4 on monoamine neurons have been analyzed by chemical assay of endogenous monoamines and their metabolites in rat CNS. The results confirmed that the neurotoxic action of DSP 4 is predominantly on noradrenaline nerve terminal projections originating from locus coeruleus, with the most marked effects on terminal fields localized most distant from the noradrenaline perikarya. DSP 4 treatment (10 days) caused no alteration of the regional DA levels, except in cingulate cortex, where a moderate increase (+40%) was observed, possibly at least partially related to a sprouting of dopamine nerve terminals following the noradrenaline denervation. 5-hydroxytryptamine levels were generally unaltered after DSP 4, except for an about 10-25% reduction in cerebral cortex and hippocampus. There was with time a certain noradrenaline recovery, most likely related to regeneration of noradrenaline nerve terminals, although this process was relatively slow (months). Analysis of catecholamine decline after tyrosine hydroxylase inhibition and metabolite/monoamine ratios, as indices for transmitter utilization rate, indicated an increased noradrenaline turnover in terminals spared by DSP 4, while dopamine turnover appeared to be reduced in many regions (i.a. cerebral cortex, striatum, accumbens, olfactory tubercle and spinal cord), most pronounced in cingulate cortex. The results indicate that noradrenaline neurons have a facilitatory action on dopamine neurons. The DSP 4 treatment did not cause any significant effect on 5-hydroxytryptamine turnover in any of the individual regions analyzed.
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PMID:Effects of the noradrenaline neurotoxin DSP 4 on monoamine neurons and their transmitter turnover in rat CNS. 620 23

An overall schema for the synaptic interactions of monoaminergic and peptidergic neurons and their relation to the ventricle and to blood vessels within the rat area postrema is presented. The specific markers include: 1) the immunocytochemical localization of the catecholamine-synthesizing enzyme tyrosine hydroxylase, and the neuropeptides enkephalin and substance P; and 2) the radioautographic localization of [3H]serotonin (5-hydroxytryptamine) and 3H-labeled amino acids anterogradely transported from the nodose ganglion.
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PMID:Ultrastructural localization of monoamines and peptides in rat area postrema. 620 70

The preovulatory surge of luteinizing hormone reaches a maximum at 18.00 h on the day of pro-oestrus in female rats maintained with regular lighting from 06.00 to 20.00 h. This surge is initiated by a discharge of luteinizing hormone-releasing hormone into hypophysial portal blood. In this study, drugs which affect catecholamine-mediated neurotransmission were administered on the day of pro-oestrus and the effects on serum concentrations of luteinizing hormone and on subsequent ovulation were observed. alpha-Methyl-p-tyrosine, diethyldithiocarbamate and SKF 64139 inhibit catecholamine synthesis at the level of tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, respectively. Although alpha-methyl-p-tyrosine suppressed ovulation, it had a negligible effect on the incidence of the preovulatory surge. In contrast, the various treatments with diethyldithiocarbamate and SKF 64139 resulted in a minimal occurrence of the 18.00 h surge; at relatively low doses, however, these drugs frequently elicited a surge at 22.00 or 24.00 h which invariably resulted in ovulation. The failure of the surge after diethyldithiocarbamate or SKF 64139 was not associated with a loss of pituitary sensitivity to luteinizing hormone-releasing hormone. In terms of the hypothalamic concentration of dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine at 18.00 h on pro-oestrus, the only common effect of diethyldithiocarbamate and SKF 64139, given in a dose which blocks the surge, was a severe depletion of adrenaline; alpha-methyl-p-tyrosine failed to produce this effect despite inducing a marked depression of dopamine and a moderate loss of noradrenaline. Neither the increase in hypothalamic dopamine after diethyldithiocarbamate, nor the alpha 2 receptor blocking properties of SKF 64139 appear to be relevant in this context since injections of L-dopa or piperoxane, an alpha 2 receptor antagonist, were without effect on the surge or ovulation. The failure of the surge after prazosin, an alpha 1 receptor antagonist, indicates that the function of adrenaline may be mediated postsynaptically by alpha 1 receptors. Clonidine, an alpha 2 receptor agonist which reduces the turnover rate of hypothalamic adrenaline, had effects of the surge and ovulation which were comparable to those of diethyldithiocarbamate and SKF 64139, the relatively low doses causing some of the surges to occur at 24.00 instead of 18.00 h and higher doses suppressing the surge at both times and thus preventing ovulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of manipulating catecholamines on the incidence of the preovulatory surge of of luteinizing hormone and ovulation in the rat: evidence for a necessary involvement of hypothalamic adrenaline in the normal or 'midnight' surge. 635 42

Subchronic (5 mg/kg SC, twice daily for 14 days) but not acute administration of the beta-2-adrenoceptor agonist salbutamol to rats caused a significant increase in the accumulation of 5-hydroxytryptophan in the limbic forebrain, the corpus striatum and the cerebral cortex when measured during 30 min after inhibition of L-amino acid decarboxylase by NSD 1015 (100 mg/kg IP). Simultaneously assayed tryptophan concentrations in the same brain regions were not affected. These results indicate an increase in the in vivo rate of tryptophan hydroxylation in the brain, produced by subchronic salbutamol administration. The effect of salbutamol treatment on brain catecholamine(CA) utilization was estimated by studying the disappearance of CA in the brain after inhibition of tyrosine hydroxylase by alpha-methyltyrosine methyl ester (H 44/68), 250 mg/kg IP, 3.5 h before sacrifice. Subchronically but not acutely administered salbutamol caused both a significant increase in endogenous noradrenaline (NA) levels and an increase NA utilization. Dopamine levels and turnover were, however, not altered by either acute or subchronic treatment. The activation, probably centrally elicited, of brain NA and 5-hydroxytryptamine systems by the subchronic salbutamol regimen supports the concept of beta-adrenoceptor mediated regulation of brain monoamine systems, and could contribute to the clinically reported antidepressant activity of beta-2-adrenoceptor agonists.
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PMID:Increased brain serotonergic and noradrenergic activity after repeated systemic administration of the beta-2 adrenoceptor agonist salbutamol, a putative antidepressant drug. 678 36

Localization of 5-hydroxytryptamine immunoreactivity was studied in the rat coeliac-superior mesenteric ganglion complex and in the porcine superior and inferior mesenteric ganglia by the indirect immunofluorescence technique. In normal rats, only 5-hydroxytryptamine immunoreactive SIF cells were seen in the coeliac-superior mesenteric ganglion complex. In the rats, pretreated with a 5-hydroxytryptamine precursor, L-tryptophan, and with a monoamine oxidase inhibitor, nialamide, a large number of 5-hydroxytryptamine-immunoreactive nerve fiber terminals were detected. In normal porcine superior and inferior mesenteric ganglia, intense 5-hydroxytryptamine immunoreactivity was found in numerous nerve fibers which were located around tyrosine hydroxylase-immunoreactive principal neurons. The origin and function of these fibers are discussed.
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PMID:5-Hydroxytryptamine-immunoreactive nerve fibers in the rat and porcine prevertebral sympathetic ganglia: effect of precursor loading and relation to catecholaminergic neurons. 747 20

After pargyline treatment the turnover rates of dopamine (DA), noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-hydroxytryptamine (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) has been measured in control and aged hippocampus of the rats. In addition, the tyrosine hydroxylase (TH) activity and monoamine oxidase-A and monoamine oxidase-B activities have also been studied. The TH activity did not change in aged hippocampus as compared to controls. The monoamine oxidase-B: monoamine oxidase-A ratio increased in 26-month-old rats compared with controls. The turnover of DA, DOPAC and NA did not show significant changes while 5-HT synthesis, 5-HT accumulation rate and 5-HIAA turnover increased in aged rats. Serotonin fibers showed morphological dissimilarities between the hippocampus of young and aged rats using immunocytochemistry techniques. In aged rats aberrant serotoninergic fibers mainly appear in the molecular layer of the dentate gyrus and molecular of the hippocampal CA1. It is suggested that the aberrant morphology of 5-HT fibers may reflect the local degeneration of serotoninergic hippocampal afferents during aging. Increase of 5-HT turnover in aged might be a signal of degeneration.
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PMID:Age-related changes on monoamine turnover in hippocampus of rats. 750 92

Turnover of dopamine (DA), serotonin (5-hydroxytryptamine) (5-HT), noradrenaline (NA) and their metabolites has been measured in control and aged rats. In addition, tyrosine hydroxylase (TH) activity has been studied. After pargyline treatment, the turnover rates of DA, NA, 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), 5-HT and 5-hydroxy-3-indolacetic acid (5-HIAA) and TH activity increased in aged rats with respect to controls. At the same time the DA and 3-MT turnover increase are consistent with the hypothesis that enhanced release of DA may participate in some degenerative processes in ageing. After probenecid treatment, the turnover of homovanillic acid (HVA) was lower in aged rats than in controls. However, DOPAC turnover was higher in the aged rats. The DOPAC increase seems to indicate a reinforcement of this pathway in aged rats.
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PMID:Effect of ageing on monoamine turnover in the prefrontal cortex of rats. 751 83


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