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)

Subcellular fractionation techniques, radio-labeling by the 3H-precursor and pharmacological approach applied to the developing rat indicate the presence of at least two types of histamine-containing cells in brain. The presence of the histamine synthesizing enzyme in neurons is suggested by its developmental pattern: there is a 4- to 5-fold increase in enzyme activity from birth to adulthood, with a time-course paralleling the synaptogenesis in whole brain as well as in the 4 regions studied (medulla-pons, midbrain, hypothalamus and forebrain). As is the case for different transmitter synthesizing enzymes such as tyrosine hydroxylase, there is a shift in the subcellular distribution of histidine decarboxylase (H.D.) activity from the soluble fraction at birth to the synaptosomal fraction in the adult brain. On the other hand, several lines of evidence indicates that a portion of histamine is localized, at least in the noenatal rat brain, in mast cells: (a) the high level of histamine in the neonatal rat brain is, like in peripheral mast-cells, associated with a low enzyme activity; (b) the half-life of [3H]histidine injected s.c. at birth was about 4 days, a value close to that found in skin (a tissue rich in mast cells), but contrasting with that in adult brain (less than 1 h); (c) after subcellular fractionation, the endogenously formed [3H]histamine was recovered in the crude nuclear fraction as was the amine from peritoneal mast cells added to the brain homogenate; (d) the mast cell degranulators, compound 48/80 and polymyxin B, induce a small but significant release of the amine from incubated neonatal brain slices. Thus it appears that cerebral histamine is localized in at least two cell types. Its presence in neurons is compatible with a neurotransmitter function and its release from mast cells might represent some primitive form of cell-to-cell communication.
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PMID:Histamine synthesis in the developing rat brain: evidence for a multiple compartmentation. 110 98

By screening of culture filtrates of fungi and streptomyces for activity in inhibit dopa decarboxylase the following isoflavone compounds were obtained: psi-tectorigenen (I), genistein (II), orobol (IV), 8-hydroxygenistein (V) and a new compound (III). III was elucidated to be 3', 4', 5, 7-tetrahydroxy-8methoxy isoflavone. Among these isoflavones, IV and III showed the strongest activity in inhibiting dopa decarboxylase. All these isoflavones also inhibited histidine decarboxylase and catechol-O-methyltrasnferase. Activities of these compounds to inhibit tyrosine hydroxylase and dopamine beta-hydroxylase were examined. Orobol which showed no or only slight inhibition of tyrosine hydroxylase and dopamine beta-hydroxylase exhibited a significant hypotensive effect on spontaneously hypertensive rats.
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PMID:Isolation of isoflavones inhibiting DOPA decarboxylase from fungi and streptomyces. 120 8

The localization of 5-hydroxytryptamine (5-HT), histamine and histidine decarboxylase (HDC), the enzyme synthesizing histamine, was studied in the rat major pelvic and coeliac-superior mesenteric ganglia by an indirect immunofluorescence technique. Small cells (10-20 microns in diameter) exhibiting 5-HT, histamine or HDC immunoreactivities were observed in clusters or occurred as solitary cells in both ganglia. In the major pelvic ganglia, solitary histamine-immunoreactive principal neurons were also observed. Colocalization studies indicated that all 5-HT-, histamine- and HDC-immunoreactive small cells in these ganglia were labelled with tyrosine hydroxylase (TH), suggesting that they are small intensely fluorescent (SIF) cells. In the coeliac-superior mesenteric ganglia, all TH-immunoreactive SIF cells were also intensely immunoreactive for 5-HT and HDC. In the major pelvic ganglia, all TH-immunoreactive SIF cells contained 5-HT immunoreactivity, and the majority of them were also intensely immunoreactive for HDC. In both ganglia, however, only a subpopulation of TH-immunoreactive SIF cells displayed histamine immunoreactivity. The results indicate that in the rat major pelvic and coeliac-superior mesenteric ganglia, a population of catecholamine-containing SIF cells contain 5-HT and histamine suggesting a diverse role SIF cells may have in so far as modulation of ganglion transmission is concerned.
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PMID:Immunohistochemical localization of 5-hydroxytryptamine, histamine and histidine decarboxylase in the rat major pelvic and coeliac-superior mesenteric ganglion. 170 73

The coexistence of histamine, histidine decarboxylase (the enzyme synthesizing histamine), 5-hydroxytryptamine and tyrosine hydroxylase (the rate-limiting enzyme in catecholamine synthesis), was studied in the rat superior cervical ganglion with the indirect immunofluorescence method. Possible colocalization was examined by staining consecutive sections with two different antibodies, or alternatively in the same section by eluting the first antibody with a mild solution containing potassium permanganate and sulphuric acid, and by staining the same section with another antibody. It was shown that tyrosine hydroxylase immunoreactivity was found both in large principal nerve cells and in small cells, which on the basis of their size and high nucleus-cytoplasm ratio corresponded to small intensely fluorescent (SIF) cells. Histamine, histidine decarboxylase and 5-hydroxytryptamine immunoreactivities were observed only in SIF cells. Those SIF cells which were immunoreactive for histamine, histidine decarboxylase or 5-hydroxytryptamine also contained tyrosine hydroxylase immunoreactivity. On the other hand, all tyrosine hydroxylase-immunoreactive SIF cells were also immunoreactive for histidine decarboxylase or 5-hydroxytryptamine. Some of the SIF cells, which were non-reactive for histamine, were immunoreactive for tyrosine hydroxylase.
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PMID:Immunocytochemical colocalization of histamine, histidine decarboxylase, 5-hydroxytryptamine and tyrosine hydroxylase in the superior cervical ganglion of the rat. 288 1

Histamine releases catecholamines and opioids in primary cultured bovine adrenal medullary (BAM) chromaffin cells. We have studied whether histamine is synthesized and localized in BAM cells, and whether it can be released upon activation with secretagogues. In BAM cells histamine is immunohistochemically co-localized with tyrosine hydroxylase in 45 +/- 8% of all cells. Only histamine immunoreactivity was observed in 8 +/- 2% of all BAM cells. No mast-cell-like cells were observed in our system. Histamine can be released from BAM cells by high potassium (56 mM K+) in a calcium-dependent manner. Compound 48/80 did not release histamine from BAM cells but nicotine caused a dose-dependent liberation of the amine. Cultured BAM cells have histidine decarboxylase activity which is inhibited by alpha-fluoromethylhistidine. These results indicate that endogenous histamine is synthesized, stored and released in BAM chromaffin cells in vitro.
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PMID:Endogenous histamine in cultured bovine adrenal chromaffin cells. 750 70

The CNS monoamine cell groups that project to the pancreatic parasympathetic preganglionic neurons were identified with the use of the viral retrograde transneuronal labeling method. Pseudorabies virus (PRV) was injected into the pancreas of C8 spinal rats and subsequently, transneuronally-labelled central monoamine neurons were mapped in brain tissue sections that had been stained by an immunohistochemical procedure that allowed for the visualization of PRV products and biogenic amine neurotransmitter enzymes or serotonin (5-HT) in the same neuron. The enzymes studied were tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT), and histidine decarboxylase. Pancreatic vagal motor neurons originate exclusively from the dorsal vagal motor nucleus and some of these may be dopamine neurons because they were TH immunopositive, but DBH and PNMT immunonegative. Transneuronally labeled aminergic neurons were found throughout the medulla oblongata. The adrenergic inputs arose from the C1, C2, and C3 cell groups. Noradrenergic inputs originated predominantly from the A5 cell group, with lesser contributions from the A1 and A2 cell groups as well as from the area postrema. None of the other CNS catecholamine cells were labeled, except for some weakly staining TH-immunoreactive neurons, presumably dopaminergic, in the paraventricular hypothalamic nucleus (PVN). The greatest number of 5-HT neurons that innervate the pancreatic vagal motor neurons come from the gigantocellular reticular nucleus, pars alpha with lesser inputs from the raphe magnus, obscurus, and pallidus nuclei. None of the CNS histaminergic cell groups were labeled.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CNS monoamine cell groups projecting to pancreatic vagal motor neurons: a transneuronal labeling study using pseudorabies virus. 751 22

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

Monoamine oxidases A and B (MAO-A and MAO-B) oxidatively deaminate neurotransmitter and xenobiotic amines. The cellular localization of these isoenzymes in the central nervous system (CNS) differs markedly and only partly reflects the distribution of their presumed natural substrates. In the present study, by using in situ hybridization with 35S-labelled oligonucleotide probes, we examined the distribution of mRNAs encoding MAO-A and MAO-B in the rat CNS. Probes for tyrosine hydroxylase, histidine decarboxylase, and tryptophan hydroxylase mRNAs were used to demonstrate the catecholaminergic, histaminergic, or serotoninergic nature of some cell populations in adjacent sections. The radioligands [3H]-Ro 41-1049 and [3H]lazabemide (reversible and selective inhibitors of MAO-A and MAO-B, respectively) were used to reveal the protein distribution by enzyme radioautography. The distribution and abundance of transcripts for both isoenzymes in the tissues investigated differed markedly but, in general, correlated with the protein distribution. MAO-A mRNA and protein were most abundant in noradrenergic neurons. However, moderate levels of transcript expression and protein were also detected in the serotoninergic neurons, and low but significant levels were detected in the dopaminergic neurons. An unexpectedly remarkable degree of hybridization signal was apparent in nonaminergic cell populations, e.g., in the cerebral cortices, the hippocampal formation (CA1-3, dentate gyrus), the cerebellar granule cell layer, and the spinal cord motoneurons. In contrast, MAO-B mRNA and protein were most abundant in serotoninergic and histaminergic neurons, Bergmann glial cells, and circumventricular organs, including the ependyma. MAO-B transcripts were also weakly expressed in nonaminergic cells, e.g., in the hippocampal formation (CA1-2). A further nonneuronal localization of MAO-B transcripts was also resolved, e.g., in the glia limitans, the olfactory nerve layer, and the cerebellar peduncle. These findings reveal further the potential of various cell populations to synthesize the isoenzymes, and homologous (aminergic) and heterologous (nonaminergic) patterns of expression as well as coexpression of MAO mRNAs are described.
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PMID:Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system. 884 23

Carotid bodies harboring sensor cells for oxygen have a strategic location at the bifurcation of the carotid artery, which supplies the brain. Upon arterial hypoxia they transmit signals to the respiratory center, which increases the frequency of breathing. Dopamine is considered as the predominant transmitter of the rat carotid body sensor cells. Here we show that the rat carotid body sensor cells are the first cell type known to have the complete apparatus to synthesize, store and release both dopamine and histamine. The tyrosine hydroxylase positive dopaminergic sensor cells of juvenile rats express the histamine biosynthesis enzyme, histidine decarboxylase. Moreover, the sensor cells have not only vesicular monoamine transporter 1 (VMAT1) transporting catecholamines but also VMAT2, which is highly specific for histamine. Additionally, we found that these cells possess components of the neuroendocrine exocytosis apparatus, synaptosome-associated protein of 25 kDa (SNAP 25) and syntaxin1. The amount of histamine determined in the rat carotid body (164 pmol/carotid body) is more than 10-fold higher compared with that of dopamine. As a main effect, hypoxia significantly increased histamine release from isolated rat carotid bodies as it has been shown for dopamine. Finally, RT-PCR experiments indicate the presence of histamine receptors H1, H2 and H3 in the carotid body. Our data suggest that histamine is synthesized, stored and released upon hypoxia by dopaminergic sensor cells of the rat carotid body.
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PMID:Evidence for histamine as a transmitter in rat carotid body sensor cells. 1544 82

Previous studies have suggested that brain histamine is involved in the pathogenesis of Parkinson's disease (PD), but the role of endogenous histamine in the degeneration of dopaminergic neurons in the substantia nigra pars compact (SNpc) remains unclear. We aimed to investigate this issue by changing the brain histamine levels by giving histaminergic agents, and administrating histamine receptor antagonists in the PD animal model, i.e. the 6-hydroxydopamine (6-OHDA)-lesioned rat. In saline-treated animals, 6-OHDA infusion produced a progressive increase in apomorphine-induced turning rate and a loss of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the SNpc. Histaminergic agents were given prior and daily for 1, 7 or 14 days after 6-OHDA infusion. Histidine (500 mg/kg, i.p.), a precursor of histamine, increased the turning rate (27% on day 7 and 26% on day 14, respectively; P<0.05) and also the loss of TH-ir neurons, but only on day 1 and 7 (67% vs 47% and 90.4% vs 74% loss, respectively; P<0.05). In contrast, alpha-fluoromethylhistidine (alpha-FMH, 25 microg, i.c.v.), an irreversible inhibitor of histidine decarboxylase (HDC), significantly decreased the turning rate (25% on day 7 and 26% on day 14, respectively; P<0.05) and prevented the loss of TH-ir neurons, also only on day 1 and day 7 (28% vs 47% and 58% vs 74% loss, respectively; P<0.05). In addition, the histamine H(1) receptor antagonist pyrilamine (5 microg, i.c.v.), but not the H(2) receptor antagonist cimetidine (5 microg, i.c.v.), also decreased the turning rate (38% on day 7 and 21% on day 14, respectively; P<0.05) and prevented the loss of TH-ir neurons on day 1 and day 7 (38% vs 51% and 60% vs 78% loss, respectively; P<0.05). On day 14 after 6-OHDA lesion, there were no significant differences in the number of TH-ir neurons among all the different treatment groups. Taken together, these findings indicate that endogenous histamine may accelerate the degeneration of dopaminergic neurons via its H(1) receptor, while attenuation of histamine transmission may play a protective role on it in the early stage of development of 6-OHDA lesioned PD rats.
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PMID:Involvement of brain endogenous histamine in the degeneration of dopaminergic neurons in 6-hydroxydopamine-lesioned rats. 1791 65


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