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)

[3H]-Flunitrazepam (FNT) binding was measured in the post-mortem brains of 13 chronic schizophrenics and 10 controls whose mean ages and death-to-freezing intervals were the same in each group. The specific binding of [3H]-FNT to the medial frontal cortex, orbitofrontal cortex, orbital cortex, medial and inferior temporal gyri, superior temporal gyrus, cornu Ammonis 1-3 and putamen was significantly higher in schizophrenics than in controls. Specific binding to the eye movement area (frontal eye field), motor cortex, lateral occipitotemporal gyrus, dentate gyrus of the hippocampus and secondary and tertiary visual cortex did not differ in the two groups. Type 1 benzodiazepine (BZ) binding sites in the superior temporal gyrus of schizophrenics, determined from the displacement of [3H]-FNT binding using a triazolopyridazine, CL 218,872 (200 nM), were significantly higher than in the control group. The increase in type 2 BZ binding sites was not significant. Antipsychotic or benzodiazepine medication did not appear to affect the results. There were significant correlations between specific [3H]-FNT binding and concentration of GABA (positive) and of glutamic acid (negative), specific [3H]-kainic acid binding (positive), activity of tyrosine hydroxylase (positive), and substance P-like immunoreactivity (positive) in many areas of the brain. The Bmax of [3H]-spiperone binding in the putamen was also correlated positively with specific [3H]-FNT binding. These data suggest that dysfunction of BZ receptors may be involved in the pathogenesis and some symptoms of chronic schizophrenia.
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PMID:Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics. 255 17

It has been previously demonstrated that nigrostriatal dopaminergic fibres participate in the neural regulation of the activity of adrenal tyrosine hydroxylase, specifically in its induction. To determine whether activation or inhibition of these fibres is responsible for this induction, the role of presynaptic dopamine receptors was investigated. Apomorphine (0.2 mg/kg), (+)3-PPP (10 mg/kg) and BHT 920 (1-3 mg/kg), drugs that are reported to bind to presynaptic dopamine receptors and thereby inhibit the release of that neurotransmitter, caused significant increases in the activity of the enzyme. As a central GABA (gamma-aminobutyric acid) system is believed to exert inhibitory control over the release of dopamine, GABA agonists were also tested for their effects. Muscimol (3 mg/kg), gamma-hydroxybutyrate (500 mg/kg) and HA-966 (150 mg/kg) produced significant induction of the adrenal enzyme; this induction was not blocked by dopamine postsynaptic receptor antagonists. After intraventricular administration (5 micrograms/rat) in normal animals, HA-966 produced significant induction of tyrosine hydroxylase. Its systemic administration did not induce the enzyme in animals with the adrenal denervated. When administered together at submaximal doses, HA-966 and BHT 920 produced an additive effect in the induction of adrenal tyrosine hydroxylase.
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PMID:Central regulation of adrenal tyrosine hydroxylase: interaction between dopamine and GABA systems. 256 51

It is established that GABA interacts with tyrosine hydroxylase through the allosteric site which is not identical to sites of tyrosine, DOPA, pterin cofactor, dopamine binding. This interaction is very significant in the GABA influence on the regulation of the tyrosine hydroxylase activity by presynaptic receptors. GABA is supposed to be able to cause dissociation of oligomeric forms of tyrosine hydroxylase.
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PMID:[Regulation of tyrosine hydroxylase activity in the rat hypothalamus with gamma-aminobutyric acid]. 256 79

Corticotropin-releasing factor (CRF) and dopamine (DA) are important integrators of the endocrine and autonomic response to stress. CRF neurons in the anterior portions of the periventricular nucleus (PV) and parvocellular paraventricular nucleus (pvPVN) occur close to A14 DA neurons in these same locations. Since CRF has been shown to act as an excitatory neurotransmitter, possible CRF interactions with the DA system were investigated using double-label immunocytochemistry. Coronal vibratome sections through the PV and pvPVN were obtained from colchicine-treated and nontreated juvenile female cynomolgus macaques. They were sequentially immunostained for tyrosine hydroxylase (TH) (to identify DA neurons) with PAP and DAB, and for CRF using 15 nm colloidal gold. By light microscopy, areas of coincidence of TH- and CRF-immunoreactive cell bodies in the PV and pvPVN were obvious, but double-stained elements were not observed. By electron microscopy, asymmetrical synapses frequently occurred between CRF axons and TH dendrites or somata. Symmetrical axosomatic synapses sometimes appeared adjacent to these CRF/TH synapses, while symmetrical axoaxonic synapses were rare. We conclude that CRF neuronal efferents synaptically activate A14 DA neurons in the primate PV and pvPVN. Parallel CRF/DA symmetrical synapses also suggest coexistence of a companion transmitter within some of these same CRF neurons. Our own previous work and recent independent studies indicate that this transmitter is probably GABA. Thus the CRF neuronal system, which is known to alter secretion of several pituitary hormones, may also act through hypothalamic periventricular DA neurons to mediate other responses to stress.
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PMID:Corticotropin-releasing factor neurons innervate dopamine neurons in the periventricular hypothalamus of juvenile macaques. Synaptic evidence for a possible companion neurotransmitter. 257 55

Employing fluorescent retrograde double/triple labeling techniques, we found that a substantial population of substantia nigra pars reticulata cells send divergent axon collaterals to both the ipsilateral striatum and bilateral superior colliculi in the rat. These multi-collateralized neurons were localized predominantly in the ventrolateral portion of the substantia nigra pars reticulata at its rostral level. Furthermore, tyrosine hydroxylase immunofluorescence histochemistry combined with fluorescent retrograde tracing techniques showed that the vast majority (more than 85%) of such specifically branched cells are dopaminergic. This novel nigral cell population seems to be in a strategic position to evoke dopamine-mediated motor impairments (i.e. abnormal saccadic eye movements in Parkinsonism) and/or behavioral syndromes (i.e. compulsive turning behavior) through the GABA-containing nigrotectal pathway.
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PMID:Bilateral tectal projection of single nigrostriatal dopamine cells in the rat. 257 13

Immunohistochemical techniques were used to survey the distribution of several conventional transmitters, receptors, and neuropeptides in the pigeon nucleus of the basal optic root (nBOR), a component of the accessory optic system. Amongst the conventional neurotransmitters/modulators, the most intense labeling of fibers/terminals within the nBOR was obtained with antisera directed against glutamic acid decarboxylase (GAD) and serotonin (5-HT). Moderately dense fiber plexuses were seen to label with antibodies directed against tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). GAD-like immunoreactivity (GAD-LI) was found in many small and medium-sized perikarya within the nBOR. Some of the medium-sized cells were occasionally positive for ChAT-LI. Cell body and dendritic staining was also commonly seen with the two tested antisera against receptors-anti-GABA-A receptor and anti-nicotinic acetylcholine receptor. The antisera directed against various neuropeptides produced only fiber labeling within the nBOR. The densest fiber plexus staining was observed with antiserum against neuropeptide Y (NPY-LI), while intermediate fiber densities were seen for substance P (SP-LI) and cholecystokinin (CCK-LI). A few varicose fibers were labeled with antisera against neurotensin (NT), leucine-enkephalin (L-ENK), and the vasoactive intestinal polypeptide (VIP). Unilateral enucleation produced an almost complete elimination of TH-LI in the contralateral nBOR. SP-LI and CCK-LI were also decreased after enucleation. No apparent changes were seen for all other substances. These results indicate that a wide variety of chemically-specific systems arborize within the nBOR. Three of the immunohistochemically defined fiber systems (TH-LI, SP-LI, and CCK-LI fibers) were reduced after removal of the retina, which may indicate the presence of these substances in retinal ganglion cells. In contrast, the fibers exhibiting ChAT-LI, GAD-LI, 5-HT-LI, NPY-LI, NT-LI, L-ENK-LI, and VIP-LI appear to be of nonretinal origin. Two different populations of nBOR neurons exhibited GAD-LI and ChAT-LI. However, these two populations together constituted only about 20% of the nBOR neurons.
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PMID:Neurotransmitters, receptors, and neuropeptides in the accessory optic system: an immunohistochemical survey in the pigeon (Columba livia). 257 70

The release of endogenous dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) was measured in superfused striatal slices of the rat and the results compared with data obtained for the release of endogenous (a) DA and DOPAC in the cerebral cortex, nucleus accumbens and thalamus; (b) 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), GABA, and glutamate in the striatum; and (c) GABA, glutamate and 5-HT in the cerebral cortex. In superfused slices of all four CNS regions, there appeared to be a Ca2+-dependent, K+-stimulated release of endogenous DA. In addition, in slices of the striatum and nucleus accumbens there also appeared to be a Ca2+ -dependent, 60 mM K+ stimulated release of endogenous DOPAC. In the striatum, 16 mM Mg2+ was as effective as 2.5 mM Ca2+ in promoting the 60 mM K+-stimulated release of DOPAC. In addition, 16 mM Mg2+ appeared to function as a weak Ca2+ agonist since it also promoted the release of DA to approximately 40% of the level attained with Ca2+ in the presence of 60 mM K+. On the other hand, in the striatum, 16 mM Mg2+ inhibited the Ca2+-dependent, 60 mM K+-stimulated release of GABA and glutamate. Similar Mg2+-inhibition was observed in the cerebral cortex not only for GABA and glutamate but also for DA and 5-HT. With the use of alpha-methyl rho-tyrosine (tyrosine hydroxylase inhibitor), cocaine (uptake inhibitor) and pargyline (monoamine oxidase inhibitor), it was determined that most of the released DA and DOPAC was synthesized in the slices during the superfusion; DOPAC was not formed from DA which had been released and taken up; and DA and DOPAC were released from DA nerve terminals. In addition, the data indicate a difference in the release process between the amino acids and the monoamines from striatal slices since Mg2+ inhibited the Ca2+-dependent, K+-stimulated release of GABA and glutamate and appeared to promote the release of DA and 5-HT.
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PMID:Release of endogenous dopamine, 3,4-dihydroxyphenylacetic acid, and amino acid transmitters from rat striatal slices. 286 May 79

Two different antigens in the same ultrathin section of brain tissue can be revealed by 'double immunocytochemistry' in which one antigen is detected by horseradish peroxidase and the other by silver intensification of colloidal gold (SIG) adsorbed to Protein A. By means of this procedure it has been possible to show that GABAergic axon terminals (containing glutamate decarboxylase) are in synaptic contact with the cell bodies and dendrites of dopaminergic neurons (containing tyrosine hydroxylase) in the substantia nigra of the rat. Thus, several of the physiological and pharmacological effects of GABA and GABAergic drugs in this part of the brain are likely to be mediated by a direct action via postsynaptic GABAergic receptors located on dopaminergic nigrostriatal neurons.
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PMID:GABA axons in synaptic contact with dopamine neurons in the substantia nigra: double immunocytochemistry with biotin-peroxidase and protein A-colloidal gold. 286 17

We found that the catecholamine biosynthetic enzymes, tyrosine hydroxylase, dopamine B-hydroxylase and phenylethanolamine N-methyltransferase share similar protein domains in their primary structures, and therefore are coded for by a single gene or a family of genes. In a recent report, we also demonstrated that antisera directed against tyrosine hydroxylase, choline acetyltransferase and glutamate decarboxylase cause specific complement-mediated lysis of dopaminergic, cholinergic and GABA-ergic subpopulation of synaptosomes, respectively. This implies that the neurotransmitter biosynthetic enzyme and the specific nerve ending protein(s) also share similar protein domain(s). Therefore, we postulate that the specific neurotransmitter biosynthetic enzyme and a certain membrane protein of the nerve endings probably share similar gene coding sequences and that coordinate expression of these proteins may determine the phenotype of the neuron.
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PMID:Genes for neurotransmitter synthesis, storage and release. 286 55

Silver-intensified gold (SIG) particles were used for light- and electron-microscopic immunocytochemical localization of neuronal antigens, and the SIG method was compared with related heavy-metal methods for the purpose of dual ultrastructural localization of neurotransmitter-related antigens. SIG immunostaining was combined with peroxidase immunostaining to allow simultaneous study of differentially labeled tyrosine hydroxylase and glutamate decarboxylase immunoreactive neurons in the medial hypothalamus. A number of electron-dense markers that might be of use in double immunostaining for light and electron microscopy were examined, either with a simple nitrocellulose dot-blot method or on Formvar-coated slot grids. Of these, silver-intensified 5 nm colloidal gold was the most effective. Silver intensification of colloidal silver and of peroxidase reaction product also showed promise for combined LM and EM double-immunolabeling studies. Since the silver-intensification procedure used here intensifies both gold and peroxidase, in experiments involving, double staining, the silver-intensified gold procedure should be used for the first antigen and nonintensified HRP for the second. Presumptive dopaminergic neurons containing the enzyme tyrosine hydroxylase were located throughout the hypothalamus with SIG immunostaining. In the same areas where frequent tyrosine hydroxylase immunoreactive neurons were found, many axons and bouton terminals were also found with antisera against GABA or against the GABA-synthesizing enzyme glutamate decarboxylase. Areas containing cells immunoreactive for tyrosine hydroxylase and stained with SIG and axons immunoreactive for glutamate decarboxylase and stained with peroxidase included the periventricular area (A14), the arcuate nucleus (A12), the dorsomedial hypothalamus/zona incerta area (A13), the posterior hypothalamus (A11), the medial paraventricular nucleus, and dorsal to the supraoptic nucleus, in addition to the preoptic area near the third ventricle and dorsally adjacent to the anterior commissure. For comparison, the SIG procedure was also used to stain dopaminergic neurons outside the hypothalamus in the substantia nigra and ventral tegmental area. Double immunocytochemical staining of two different neurotransmitter-related antigens allowed examination with both light and electron microscopy. By virtue of a large silver shell formed around the colloidal gold particle and its adsorbed immunoglobulin or protein A, cross-reactivity of the first set of immunoreagents stained with particulate silver and a second set stained with peroxidase could be reduced or eliminated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tyrosine hydroxylase immunoreactive neurons throughout the hypothalamus receive glutamate decarboxylase immunoreactive synapses: a double pre-embedding immunocytochemical study with particulate silver and HRP. 287 Jan 43


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