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)

Immunocytochemical evidence is presented for the existence of choline acetyltransferase (ChoAcTase), cysteine sulfinic acid decarboxylase (CSADCase), tyrosine hydroxylase (TyrOHase), and glutamic acid decarboxylase (GluDCase) in large motor neurons of the hypoglossal nucleus and the spinal cord and in nerve terminals of motor end plates in tongue and skeletal muscle of five mammalian species, including man. These enzymes, which are responsible for the synthesis of acetylcholine (AcCho), taurine, dopamine, and gamma-aminobutyrate (GABA), respectively, were detected by immunocytochemical studies with monoclonal or polyclonal antibodies raised against the enzymes. Electron microscopy of the neuromuscular junctions showed that the immunoreactivity in each case was confined to the cytoplasmic matrix of presynaptic nerve terminals. Immunoreactivity obtained for each enzyme antibody varied with the species. It was highest in fresh, unfixed muscle and lowest in aldehyde-fixed specimens. Negative controls were obtained with preimmune sera and antisera preabsorbed with pure ChoAcTase, CSADCase, or GluDCase antigen. Double-labeling studies with ChoAcTase antibodies and acetylcholinesterase (AcChoEase) antibodies, AcChoEase enzyme activity, or alpha-bungarotoxin binding indicated that ChoAcTase, AcChoEase, and AcCho receptors were colocalized at the same end plates.
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PMID:Synthesizing enzymes for four neuroactive substances in motor neurons and neuromuscular junctions: light and electron microscopic immunocytochemistry. 612 35

Dopaminergic and GABAergic neurons were visualized in the same section of rat substantia nigra (SN) and zona incerta (ZI) by a two-color double immunoperoxidase procedure or by double immunofluorescence. Rabbit antiserum to tyrosine hydroxylase (TH) and sheep antiserum to glutamic acid decarboxylase (GAD), markers for catecholaminergic and GABAergic neurons, respectively, were used as primary antisera. These techniques rely on species difference of primary antisera and non-crossreactivity of linking antisera. In normal and colchicine pretreated rats, SN pars compacta (SNC), SN pars lateralis (SNL), and ZI pars medialis (area A13) contained high densities of TH-positive neurons. Relatively few TH-positive cells were scattered in SN pars reticulata (SNR) and ZI pars lateralis (ZIL). In normal rats, GAD-positive boutons were more numerous throughout SNR and ZIL than in SNC, SNL, and area A13. In colchicine pretreated rats, the majority of neurons in SNR and ZIL and few neurons in SNC, SNL, and area A13 were GAD-positive and TH-negative. This study suggests a dichotomy of both SN and ZI into a predominantly dopaminergic and a predominantly GABAergic part.
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PMID:Two-color immunohistochemistry for dopamine and GABA neurons in rat substantia nigra and zona incerta. 612 46

The content of gamma-aminobutyric acid (GABA) and the activities of glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) were measured in whole putamen obtained at autopsy from 13 patients dying with idiopathic Parkinson's disease and 13 appropriate control subjects. Mean GABA content was significantly elevated (by 28%) in the putamen of the Parkinson's disease patients. TH activity was markedly reduced, while there was no significant reduction of GAD activity in the putamen of these patients. GABA content was also measured in both sides of the striatum in rats which had received unilateral injections of 6-hydroxydopamine (6-OHDA) in the vicinity of the axons of the nigrostriatal projection. Mean GABA content was found significantly elevated (by 33%) in the ipsilateral striatum. Loss of dopaminergic nigrostriatal neurons, in both human Parkinson's disease and in the rat 6-OHDA model, is accompanied by increased striatal GABA content. The assumption that GABAergic neurotransmission is reduced in the striatum in Parkinson's disease may not be correct.
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PMID:Striatal GABAergic neuronal activity is not reduced in Parkinson's disease. 613 32

Behavioural and biochemical studies were carried out in rats given a single daily dose (1 mg/kg, i.p.) of haloperidol for 30 days and subsequently withdrawn for 7 days. Long-term administration of haloperidol resulted in supersensitivity of dopamine receptors. This was manifested by enhanced stereotypic biting, rearing, locomotor and floor activity of haloperidol withdrawn rats when challenged to a low dose of apomorphine (0.5 mg/kg, s.c.) on the 8th day. Chronic haloperidol treatment significantly decreased dopamine synthesis and release as evidenced by low activity of tyrosine hydroxylase and low level of homovanillic acid in striatum. Dopamine levels did not change in the frontal cortex, striatum and midbrain. Haloperidol treatment significantly increased striatal gamma-aminobutyric acid content and glutamic acid decarboxylase activity by 17% and 16% respectively. The decreased tyrosine hydroxylase activity and homovanillic acid level in corpus striatum might, in part, be due to an inhibitory effect of GABAergic neurons on dopaminergic system. Rats withdrawn from chronic haloperidol treatment showed significant increases in GABA level and glutamic acid decarboxylase activity. This probably resulted in further inhibition of dopamine release as evidenced by marked accumulation of dopamine in the corpus striatum and midbrain. No significant alterations in the endogenous levels of norepinephrine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were observed in haloperidol-treated and subsequently withdrawn rats. These data suggest that chronic haloperidol treatment and subsequent withdrawal results in the development of behavioural dopamine supersensitivity as well as biochemical alterations in dopaminergic and GABAergic system. The changes in these two neuronal systems seem to be interrelated.
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PMID:Behavioural and biochemical alterations following haloperidol treatment and withdrawal: the animal model of tardive dyskinesia reexamined. 613 27

Activities of the neurotransmitter synthetic enzymes, choline acetyltransferase (EC 2.3.1.6; ChAT), glutamic acid decarboxylase (EC 4.1.1.15; GAD), and tyrosine hydroxylase (EC 1.14.3.2; TH), were assayed in four brain regions of A/J and C57BL/6J mice at three ages (4, 18, and 24 months). The brain regions assayed were the fronto-parietal cortex, hippocampus, striatum, and cerebellum. Strain effects: In some brain regions, at several ages, ChAT activity did not differ among the two strains. However, ChAT was higher in the C57BL/6J strain in the cortex at 18 months, the hippocampus at 18 and 24 months, the striatum at 24 months, and the cerebellum at 4 months. The reverse was true in the cerebellum at 24 months, where ChAT was higher in A/J mice. GAD activity in C57BL/6J mice compared to that of A/J mice was higher in the striatum and cortex, and lower in the hippocampus and cerebellum. TH activities in all four regions were generally higher in C57BL/6J mice than in A/J mice. Age effects: Age differences in enzyme activities varied with the genetic strain. ChAT activity generally was higher in brain regions of older mice of both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age and strain comparisons of neurotransmitter synthetic enzyme activities in the mouse. 613 17

Immunohistochemical double staining for gonadotropin releasing hormone (GnRH) and tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD) reveals in the septo-preoptic-diagonal band complex of the rat brain close spatial associations between GnRH-immunoreactive perikarya and TH and GAD immunoreactive fibers. In the organum vasculosum laminae terminalis, no close spatial relationships could be observed between TH- or GAD-positive fibers and the GnRH-containing system. In contrast, in the median eminence substantial overlap exists in the distribution of GnRH with TH and GAD containing nerve fibers. This overlap is most intense for TH throughout the lateral palisade zone, while for GAD it is more restricted to the outermost portion of the external palisade zone. The results suggest that dopamine and GABA influence GnRH secretion via axosomatic contacts in the septo-preoptic-diagonal band complex, as well as via axo-axonic interactions in the median eminence, while no such interactions seem to exist in the organum vasculosum laminae terminalis. Since dopaminergic cell bodies in the ventral hypothalamus are closely apposed by GnRH and GAD containing fibers, the existence of feedback circuits among GnRH, dopamine and GABA systems is proposed.
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PMID:Anatomical relationships of dopaminergic and GABAergic systems with the GnRH-systems in the septo-hypothalamic area. Immunohistochemical studies. 613 90

Immunocytochemistry enables the localization of transmitter-related antigens in tissue sections at either the light microscopic or the electron microscopic level. In the case of neuropeptides and certain transmitters (e.g. serotonin) it has been possible to produce antibodies directed against the putative transmitter itself. In other cases it has not been possible to produce useful antibodies against transmitters but antibodies have been raised against enzymes involved in transmitter metabolism (e.g. tyrosine hydroxylase, glutamic acid decarboxylase) and these antibodies are suitable markers for transmitter systems. Successful immunostaining with an antibody depends on a number of factors, two of the most important being the fixation of the antigen in the tissue and the visualization of the primary antibody once it has bound to the antigen. Techniques available for the visualization of bound primary antibody include the indirect-labelled immunofluorescence procedure and the unlabelled peroxidase-antiperoxidase (PAP) procedure. Direct-labelled immunocytochemistry is not now widely used but is likely to become increasingly important with the introduction of monoclonal antibodies and the development of techniques for the simultaneous localization of multiple antigens. Monoclonal antibody procedures also allow the production of antibodies against antigens which are difficult to purify such as certain transmitter markers (e.g. choline acetyltransferase) and constituents of neuronal membranes. Immunocytochemistry allows the production of detailed maps of the distribution of putative transmitters in the nervous system and in combination with tract tracing procedures is being used increasingly to identify transmitters in neuronal circuits. It has also been important in establishing the transmitter status of various neuroactive compounds in single neurones. Immunocytochemistry can be carried out on post-mortem samples and is providing information on transmitter distribution in normal and abnormal human brain.
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PMID:Immunocytochemistry and neurobiology. 613 41

Five enzymes involved in glutamic acid, GABA, and catecholamine metabolism were measured in epileptic human brain. Electrocorticographically defined areas of focal spiking were compared with samples from surrounding nonspiking cortex. Comparative enzyme activities were as follows (mumol/h/g wet wt): glutamic acid dehydrogenase (GDH)--spiking 135.77 +/- 10.22 (mean +/- SEM), nonspiking 118.58 +/- 9.42 (p less than 0.001, N = 17); glutamic acid decarboxylase--spiking 10.63 +/- 0.95, nonspiking 9.96 +/- 1.10 (NS, N = 13); GABA-aminotransferase--spiking 36.49 +/- 1.05, nonspiking 36.46 +/- 1.48 (NS, N = 12); glutamine synthetase--spiking 96.94 +/- 3.81, nonspiking 96.52 +/- 4.10 (NS, N = 20); and tyrosine hydroxylase (TH; nmol/h/g)--spiking 16.23 +/- 2.39, nonspiking 10.67 +/- 1.95 (p less than 0.001, N = 14). Increased activity of GDH and TH may prove useful to characterize further areas of active spiking in human focal epilepsy.
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PMID:Enzyme changes in actively spiking areas of human epileptic cerebral cortex. 614 16

The distribution of glutamic acid decarboxylase(GAD)- and tyrosine hydroxylase(TH)-like immunoreactivities in the hypothalamic arcuate nucleus of the rat was investigated using an indirect immunofluorescence technique. GAD-positive cell bodies were found in the arcuate nucleus, mainly clustered in its dorsomedial parts. A dense terminal plexus was observed in the lateral palisade zone of the median eminence. The apparent overlap of this distribution pattern with that for TH immunoreactivity was studied directly using an elution-restaining procedure. This revealed apparent coexistence of GAD- and TH-like immunoreactivities in a subpopulation of arcuate neurons. The relevance of this finding to the control of anterior pituitary secretion is discussed.
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PMID:Coexistence of tyrosine hydroxylase-like and gamma-aminobutyric acid-like immunoreactivities in neurons of the arcuate nucleus. 614 73

Adult male and female rats treated neonatally with monosodium glutamate (MSG) exhibit lesions in the arcuate nucleus of the hypothalamus. Immunohistochemical analysis of the distribution of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD), neurotensin (NT) and gonadotropin-releasing hormone (GnRH) reveals substantial destructions of tuberoinfundibular dopamine and NT systems accompanied by a marked reduction of immunoreactivity in the median eminence. GAD immunoreactivity in the arcuate nucleus and median eminence is greatly reduced, while GnRH containing structures in the mediobasal hypothalamus are not noticeably affected. Evaluation of autoradiograms after intravenously administered [3H] estradiol in the ventral hypothalamus indicate an almost complete loss of target neurons in the arcuate nucleus but not in the nearby ventromedial nucleus. The results suggest that: (a) NT- and dopamine-containing neurons of the arcuate nucleus project to the median eminence via tuberoinfundibular NT and dopaminergic pathways; (b) GABA in the median eminence originates to a major extent from neurons of the arcuate nucleus through a tuberoinfundibular GABAergic system; (c) GnRH is produced in the rat outside the arcuate nucleus; (d) the MSG-induced lesion in the basal tuberal region abolishes or strongly diminishes estradiol target neurons in the arcuate nucleus.
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PMID:Monosodium glutamate lesions in rat hypothalamus studied by immunohistochemistry for gonadotropin releasing hormone, neurotensin, tyrosine hydroxylase, and glutamic acid decarboxylase and by autoradiography for [3H] estradiol. 614 23


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