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 coexistence of S100beta with calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), nicotinamide adenosine dinucleotide phosphate-diaphorase (NADPH-d), and tyrosine hydroxylase (TH) was examined in the glossopharyngeal and vagal sensory ganglia. S100beta immunoreactive (-ir) neurons in the jugular and petrosal ganglia frequently colocalized CGRP- or SP-ir, whereas S100beta-ir neurons in the nodose ganglion infrequently contained CGRP- or SP-ir. No S100beta-ir neurons in the jugular and petrosal ganglia showed SOM-ir while the small number of SOM-ir neurons in the nodose ganglion colocalized S100beta-ir. Many neurons in the nodose ganglion colocalized S100beta-ir and NADPH-d activity, whereas S100beta-ir neurons in the jugular and nodose ganglia infrequently contained NADPH-d activity. S100beta- and TH-ir were frequently colocalized in nodose ganglion but not in petrosal or jugular ganglion neurons. These findings suggest relationships between S100beta and specific putative transmitters in functions of subpopulations of vagal and glossopharyngeal sensory neurons.
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PMID:Coexistence of s100beta and putative transmitter agents in vagal and glossopharyngeal sensory neurons of the rat. 968 88

Transiently catecholaminergic cells (TC-cells) expressing tyrosine hydroxylase (TH) have been shown in a variety of tissues during embryonic life. To investigate the possible relationship of nitric oxide synthase (NOS)-containing renal neuronal somata (RNS) and the TC-cells, we examined serial 100 microm slices of whole kidneys for TH-immunofluorescence and NADPH-d histochemistry during prenatal and postnatal development. The number of TH-cells increased during the prenatal period, peaked at birth and were very rare by PD21. A subpopulation of TH-immunoreactive RNS displayed NADPH-d activity. By PD21 the TH-positive RNS had practically disappeared while the number of NADPH-d positive RNS was markedly increased. These results suggest that kidneys possess transient catecholaminergic cells which display NOS-activity and that NOS expression may be the end-point in the differentiation of the RNS.
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PMID:Evidence for NOS-containing renal neuronal somata transiently expressing a catecholaminergic phenotype during development in the rat. 972 68

Susceptibility to develop Parkinson's disease has been linked to abnormalities of P450 enzyme function. Multiple P450 enzymes are expressed in brain but the relationship of these to Parkinson's disease is unknown. We have investigated the expression of P450 enzymes in the rat substantia nigra and their co-localization in tyrosine hydroxylase-positive neurons and astrocytes. Immunohistochemistry was performed using anti-peptide antisera against the following P450 enzymes: CYP1A1, CYP1A2, CYP2B1/2, CYP2C12, CYP2C13/2C6, CYP2D1, CYP2D4, CYP2E1, CYP3A1, CYP3A2 and NADPH-P450 oxidoreductase. Immunoreactivity in nigral cells was found only for CYP2E1 and CYP2C13/2C6. CYP2E1 immunoreactivity was localized to many midbrain nuclei including the substantia nigra pars compacta but not the substantia nigra pars reticulata while immunoreactivity to CYP2C13/2C6 was found in the substantia nigra pars compacta, substantia nigra pars reticulata and many other midbrain nuclei. Sections of rat midbrain double labelled for either CYP2E1 or CYP2C13/2C6 and tyrosine hydroxylase or glial fibrillary acidic protein were examined for co-localization by confocal laser scanning microscopy. CYP2E1 and CYP2C13/2C6 immunoreactivity was found in tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta but not in glial cells. CYP2C13/2C6, but not CYP2E1, was also found in non-glial, non-tyrosine hydroxylase-expressing cells in the substantia nigra pars reticulata. Isoniazid induction increased CYP2E1 fluorescence signal intensity from nigral dopaminergic neurons. At least two P450 enzymes are found in nigral dopamine containing cells and one, namely CYP2E1, is selectively localized to this cell population. CYP2E1 is a potent generator of free radicals which may contribute to nigral pathology in Parkinson's disease. The expression of CYP2E1 in dopaminergic neurons in substantia nigra raises the possibility of a causal association with Parkinson's disease.
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PMID:Co-localization of P450 enzymes in the rat substantia nigra with tyrosine hydroxylase. 988 65

Medullae were obtained at autopsy from seven patients with no neurologic disease, and sections were processed for tyrosine hydroxylase (TH), nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), or both. Both TH- and NADPH-d reactive neurons had close anatomical relationship with penetrating blood vessels in the ventrolateral medulla (VLM). Three patterns were identified: 1) processes arising from a neighboring neuron reaching the blood vessel; 2) direct appositions of cell bodies to blood vessels; and 3) fibers coursing parallel to the blood vessels. This intrinsic innervation may provide a mechanism of coupling among local metabolism, sympathetic activity, and blood flow in the VLM.
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PMID:Intrinsic vasomotor innervation of blood vessels in human ventrolateral medulla. 1022 13

Nitric oxide (NO) has been proposed to function as an inhibitory neurotransmitter in the lower urinary tract. This study investigates the distribution of NO-containing neurons and its changes following urethral obstruction in the guinea-pig. By using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and NO synthase (NOS) immunohistochemistry, the highest frequency of NO-containing neurons was observed in the bladder base. Double labelling studies showed that 70.9% of NADPH-d reactive neurons co-expressed NOS immunoreactivity. Acetylcholinesterase reactivity was present in the majority of the intramural neurons with 54% of them expressed NOS immunoreactivity. NADPH-d reactivity was colocalized with vasoactive intestinal polypeptide, calcitonin gene-related peptide and substance P immunoreactivities in both neurons and fibres. Colocalization study also revealed that NADPH-d reactive neurons formed a distinct cell population from tyrosine hydroxylase positive neurons. At 12 hours after urethral obstruction, NADPH-d reactivity in the intramural ganglion cells was noticeably enhanced and this was sustained till 24 hours whence some intensely stained neurons appeared to undergo degenerative changes. Neuronal degeneration was more drastic at 48 hours so that the number of NADPH-d positive neurons was significantly reduced. The present study suggests that NO is an important neurotransmitter in the urinary bladder and that it may be involved in the relaxation activity in the bladder base during micturition. It is speculated that the increased NADPH-d reactivity in intramural ganglion cells elicited by urethral obstruction may be responsible for the cell death. It is suggested that the resulting cell loss or bladder denervation may account for the urinary dysfunction such as frequency and urgency of micturition in patients with urethral obstruction.
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PMID:Nitric oxide synthase--its distribution and alteration in the intramural ganglia of the urinary bladder in normal and urethra-obstructed guinea pigs. 1037 26

Male rat copulatory ability decreases dramatically following castration. This may be due in part to the impairment of medial preoptic area (MPOA) dopamine (DA) release. Previous studies showed that extracellular DA levels in the MPOA of castrates were lower than in intact males, both during basal conditions and in the presence of a receptive female. However, tissue levels of DA in the MPOA were higher in castrates than in intact males, suggesting that DA synthesis may be normal or increased in castrates, but that release may be compromised. The current study found that neither long term (2 months) nor short term (2 weeks) castration had any effect on the number of neurons in the DA A(14) area that were immunoreactive (ir) for tyrosine hydroxylase (TH), the rate limiting enzyme for DA synthesis. Therefore, castration may not affect DA synthesis in the MPOA. Tissue levels of neurotransmitter reflect release, as well as synthesis. We previously reported that nitric oxide (NO) may increase DA release in the MPOA. The present study tested whether castration affected the number of NO producing cells in the MPOA. Long term, but not short term, castration significantly decreased the number of NADPH-d (nicotinamide adenine dinucleotide phosphate diaphorase) positive neurons and brain nitric oxide synthase immunoreactive (bNOS-ir) neurons in the medial preoptic nucleus (MPN). This suggests that in gonadally intact animals testosterone may activate NOS, which increases the production of NO. Long or short term castration had no effect on the numbers of bNOS-ir neurons in the paraventricular nucleus (PVN) or medial amygdala. However, short term castration decreased bNOS-ir neurons in the bed nucleus of stria terminalis (BNST). Thus, one means by which testosterone promotes male sexual behavior may be by increasing production of NO in the MPOA, which increases local DA release.
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PMID:Effects of testosterone on neuronal nitric oxide synthase and tyrosine hydroxylase. 1041 8

The cyto- and chemoarchitecture of basal forebrain cholinergic neurons (BFCN) was investigated in the lower primate, the common marmoset (Callithrix jacchus). A large population of magnocellular, hyperchromic, and choline acetyltransferase (ChAT)-positive neurons was detected in the marmoset basal forebrain. The distribution of these neurons was similar to those in higher primates. Thus, ChAT-positive neurons were observed in the medial septum (Ch2), the vertical (Ch2) and horizontal (Ch3) limbs of the diagonal band of Broca, and the nucleus basalis of Meynert (Ch4). The Ch4 complex was relatively well differentiated and displayed distinct sectors. We detected anterior (Ch4a, with a medial and a lateral subdivision), intermediate (Ch4i, with a dorsal and a ventral subdivision), and posterior (Ch4p) sectors in the marmoset Ch4. The Ch4i was relatively small while the Ch4p was large. Similar to the rodent, the marmoset Ch1 extended quite a distance posteriorly, and the Ch4p displayed a major interstitial component distributed within the globus pallidus, its medullary laminae, and the internal capsule. Virtually all of the marmoset BFCN displayed acetylcholinesterase activity, and low affinity (p75(NTR)) and high affinity (Trk) neurotrophin receptor immunoreactivity. A majority contained immunoreactivity for calbindin-D(28K) and calretinin. Many of the Ch4 neurons also displayed tyrosine hydroxylase immunoreactivity. The BFCN lacked galanin immunoreactivity, but were innervated by galanin-positive fibers. None of the marmoset BFCN were NADPH-d-positive. Thus, the BFCN display major anatomical and biochemical differences in the marmoset when compared with higher primates. The marmoset BFCN also display many characteristics common to other primates. This fact, combined with the relatively short life span of the marmoset, indicates that this species may be ideal for studies of age-related changes in the BFCN.
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PMID:Cyto- and chemoarchitecture of basal forebrain cholinergic neurons in the common marmoset (Callithrix jacchus). 1099 91

The histochemistry of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and immunoreactivity of neuronal nitric oxide synthase (nNOS-IR) can be demonstrated in various cell types of the vertebrate retina. In this study, we have focused on characterizing the different NADPH-d-positive amacrine cell types in turtle retina. Cryostat sections were examined by confocal laser scanning microscopy for double immunofluorescence with antibodies against nNOS and either GABA or glycine, or by combining histochemistry with immunocytochemistry to obtain triple labeling with NADPH-d, GABA, and glycine. Forty-eight percent of the NADPH-d-labeled amacrine cells colocalized GABA, 52% glycine. Here we show that two morphologically different types of amacrine cell are nNOS/glycine-IR and three types are nNOS/GABA-IR. Antibodies against calretinin, parvalbumin, somatostatin, tyrosine hydroxylase, and choline acetyltransferase did not colocalize with nNOS-IR or NADPH-d-labeled amacrine cells, but 15% of the NOS-labeled amacrine cells showed immunoreactivity against calbindin. Only GABA has been seen to colocalize with NADPH-d in amacrine cells in previous reports in other species. The finding here of glycine colocalizing with NO-containing cells is novel. We suggest that NO, apart from its well known function in gap junction regulation, can also modulate the release of both GABA and glycine in the turtle retina.
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PMID:Morphological and neurochemical diversity of neuronal nitric oxide synthase-positive amacrine cells in the turtle retina. 1107 11

To investigate how perivascular NO synthase (NOS)-containing nerves in the cerebral arterial system are involved in controlling the cerebral circulation, we observed the ultrastructure of NOS-containing nerve fibers and their terminals by means of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) histochemistry. We also observed the correlation between NADPH-d stained perivascular nerves and the perivascular sympathetic nerves, by means of double staining with NADPH-d histochemistry and tyrosine hydroxylase (TH) immunohistochemistry at the light microscopic level. NADPH-d-positive nerve fibers showed dense distribution mainly in the rostral portion of the circle of Willis and proximal portions of its main branches, where some of the NADPH-d-positive fibers coexisted with TH-positive fibers in a single nerve bundle. NADPH-d-positive nerve fibers were unmyelinated and had close contact with NADPH-d-negative myelinated and unmyelinated nerve fibers in a single nerve bundle, and NADPH-d-positive nerve terminals also existed closely with NADPH-d-negative nerve terminals. The number of NADPH-d-positive nerve terminals and their ratio to all other terminals were significantly higher in the rostral portion of the circle of Willis and the proximal portion of its branches, than the caudal portion of the circle of Willis and the distal portion of its branches. Nerve terminals were observed to locate within 250 nm from the basal lamina of arterial smooth muscle cells in the rostral portion of the circle of Willis and proximal portion of its branching arteries. The present observation confirmed that NOS-containing nerve fibers truly innervate the smooth muscle cells of the arterial wall in the circle of Willis and its main branches. Close contact between NADPH-d-positive and -negative nerve fibers and terminals in these arterial portions may indicate that NOS-containing perivascular nerves may work to modulate the rest of the other perivascular nervous system, such as the sympathetic nerves, to regulate the homeostasis of the arterial tonus.
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PMID:Ultrastructure of NADPH diaphorase-positive nerve fibers and their terminals in the rat cerebral arterial system. 1142 68

A peripheral 5-HT(2A) receptor-mediated hemodynamic change prompted formation of indole-2,3-dione, an endogenous inhibitor of atrial natriuretic peptide (ANP) receptor binding and G protein-mediated intracellular signaling (IC(50): 0.4 microM). This effect was significantly suppressed by dexamethasone, indomethacin and the 5-HT(2) receptor antagonists, ketanserin or ritanserin. 5-HT(2A) receptor-mediated acute hemodynamic change was not modified significantly by indomethacin, prazosin or propranolol pretreatment. A tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, but not a dopamine beta hydroxylase inhibitor, diethyldithiocarbamate, abolished the 5-HT(2A) receptor-mediated increase in indole-2,3-dione. Exogenous indole-2,3-dione induced a significant increase in plasma catecholamine levels and decrease in urine volume. A 5-HT(2A) receptor-mediated decrease in capillary flow may have caused an inflammatory process and peripheral sympathetic activation via ANP signaling inhibition. 3,4-dihydroxyphenylalanine (DOPA)/dopamine may contribute to the progression of inflammation or the generation of a precursor of indole-2,3-dione. The observation that indole-2,3-dione abolished angiotensin AT(1) receptor-mediated NADPH activation in both human umbilical vein endothelial cells and smooth muscle cells at 20 microM may suggest that sulfhydryl-reactive indole-2,3-dione could influence mitochondrial function and cellular redox states via flavoenzyme inhibition and/or regulation of dehydrogenase-oxidase conversion.
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PMID:Peripheral 5-HT(2A)-receptor-mediated formation of an inhibitor of atrial natriuretic peptide binding involves inflammation. 1195 86


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