Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TYROSINE DECARBOXYLASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,675 records · Page 93Linked to original sources
PubMed1989

Retroviral transfer of a human tyrosine hydroxylase cDNA in various cell lines: regulated release of dopamine in mouse anterior pituitary AtT-20 cells.

Little is known about the molecular events mediating neurotransmitter release, a crucial step in synaptic transmission. In this paper, the biosynthesis and release of L-beta-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine were analyzed in three heterologous cell lines after retroviral-mediated gene transfer of tyrosine hydroxylase (EC 1.14.16.2), the rate-limiting enzyme in catecholamine synthesis. A recombinant retrovirus encoding human tyrosine hydroxylase type I as well as neomycin-resistance gene was used to infect a fibroblast (NIH 3T3), a neuroblastoma (NS20 Y), and a neuroendocrine (AtT-20) cell line. After selection in the presence of neomycin and in tyrosine-free medium, high levels of exogenous tyrosine hydroxylase activity were detected in extracts of the three cell lines. High-performance liquid chromatography of cell extracts and culture supernatants confirmed that the three cell lines hydroxylated tyrosine to form L-DOPA and released this metabolite into the culture medium. Interestingly, the neuroendocrine cell line AtT-20 synthesized not only L-DOPA but also dopamine. Evoked secretion studies established that AtT-20 cells released the transmitter upon depolarization in a regulated, calcium-dependent way. We discuss the implication of this approach for the analyses of neurotransmitter release as well as in the context of degenerative disorders such as Parkinson disease.

Animals↗
PubMed2004

Enantio-selective inhibition of (1R,9S)- and (1S,9R)-beta-hydrastines on dopamine biosynthesis in PC12 cells.

The inhibitory effects of (1R,9S)- and (1S,9R)-enantiomers of beta-hydrastine (BHS) on dopamine biosynthesis in PC12 cells were investigated. (1R,9S)-BHS decreased the intracellular dopamine content with the IC50 value of 14.3 microM at 24 h, but (1S,9R)-BHS did not. (1R,9S)-BHS was not cytotoxic at concentrations up to 250 microM towards PC12 cells. In these conditions, (1R,9S)-BHS inhibited tyrosine hydroxylase (TH) activity mainly in a concentration-dependent manner (33% inhibition at 20 microM) and decreased TH mRNA level in PC12 cells. The inhibitory patterns of dopamine content and TH activity by (1R,9S)-BHS showed similar behavioral curves. (1R,9S)-BHS at 10-50 microM also reduced the intracellular cyclic AMP level and Ca2+ concentration. In addition, treatment of L-DOPA at 20-50 microM for 24 h increased the intracellular dopamine content to 198-251% compared with the control in PC12 cells. However, the increase in dopamine levels induced by L-DOPA (20-50 microM) was reduced when L-DOPA was combined with (1R,9S)-BHS (10-50 microM). These results indicate that (1R,9S)-BHS, but not (1S,9R)-BHS, reduced dopamine content and L-DOPA-induced increase in dopamine content, in part, through the inhibition of TH activity and TH gene expression in PC12 cells: thus, (1R,9S)-BHS proved to have a function to regulate dopamine biosynthesis.

Alkaloids↗
PubMed1992

Immunocytochemical and in situ hybridization evidence for the coexistence of GABA and tyrosine hydroxylase in the rat locus ceruleus.

We have demonstrated the coexistence of GABA-like and tyrosine hydroxylase-like immunoreactivities (GABA-LI and TH-LI, respectively) in the same neurons of the rat locus ceruleus (LC). The profiles of these cells were labeled by alternately immunostaining adjacent sections for GABA-LI or TH-LI by the avidin-biotin-peroxidase complex method or the peroxidase-anti-peroxidase method after perfusion (either Zamboni's fixative or PPG), and observation at light and electron microscopic levels. For light microscopy, pairs of adjacent sections of more than 590 (Zamboni's) and 260 (PPG), and for electron microscopy, 40 ultrathin sections cut from adjacent semithin plastic sections (Zamboni's), were examined. GABA-LI was found in 80% (1,309/1,642 in total) of small and medium-sized neurons, uniformly scattered throughout the LC. Observations unequivocally show that the majority of GABA-ergic neurons are also noradrenergic. Several neurons are neither noradrenergic nor GABA-ergic, while other noradrenergic neurons do not show GABA-LI. It is shown that astrocytes, but not oligodendrocytes, contain GABA. In situ hybridization using a probe DNA fragment of the glutamic acid decarboxylase (GAD) cDNA, amplified by the polymerase chain reaction, detected GAD mRNA signals in many neurons throughout the LC, supporting the presence of a GAD/GABA system in the LC. Multiple "classical" transmitters, including GABA, serotonin, and noradrenaline, coexist in many LC neurons and may contribute to its widely diverging projections throughout the entire CNS.

Animals↗
PubMed1991

Neuronal metabolism and DOPA decarboxylase immunoreactivity in terminal noradrenergic sympathetic axons of rat.

This study was undertaken to determine whether immuno-histochemical staining for DOPA decarboxylase (DDC) is present in axons of rat noradrenergic sympathetic neurons. A sparse plexus of varicose axons exhibiting DDC-like immunoreactivity (DDC-IR) was associated with blood vessels and acini in the submandibular gland, but this was much less extensive than the population that exhibited tyrosine hydroxylase-like immunoreactivity (TH-IR). The varicose terminal TH-IR axons in atrium, spleen, and vas deferens were devoid of DDC-IR both in grown rats and during the post-natal period of axon growth, although weak DDC-IR was seen in large pre-terminal nerve bundles. Similar patterns of staining were seen with paraffin-embedded and with frozen, formaldehyde-fixed material. No enhancement of DDC-IR was seen in any tissue after chronic alteration of catecholamine turnover with reserpine or alpha-methyl-para-tyrosine, and the numbers of submandibular DDC-IR axons were not increased by disruption of axonal transport with colchicine or by decentralization of the superior cervical ganglion. We conclude that terminal noradrenergic axons contain insufficient DDC-IR for microscopic visualization, regardless of their metabolic state, reinforcing previous evidence that DDC-IR can be used as a histochemical marker for dopaminergic axons. By this criterion, the rat submandibular gland may receive a sparse dopaminergic innervation.

Animals↗
PubMed1993

Normalization of tyrosine hydroxylase activity in vivo in the striatum of transgenic mice carrying human tyrosine hydroxylase gene: a microdialysis study.

Using a microdialysis method, we observed a similar steady-state L-3,4-dihydroxyphenylalanine accumulation in the striatum of transgenic mice carrying the human tyrosine hydroxylase (TH) gene after NSD-1015 perfusion (10(-4) M) as compared to nontransgenic mice. Basal extracellular levels of 3,4-dihydroxyphenylacetic acid before the perfusion of NSD-1015 were also comparable in both transgenic and non-transgenic striata. The results suggest that the in vivo activity of TH in the striatum of transgenic mice was retained to the normal level by some regulatory mechanism(s) in spite of the increased expression of the enzyme protein.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Localization of a defect in hypothalamic dopaminergic neurons of the aged brain that results in impaired PKA-dependent activation of tyrosine hydroxylase.

Using an in vitro incubation system, the role of the cyclic AMP-dependent protein kinase A (PKA) pathway in the regulation of the in situ activity of tyrosine hydroxylase (TH) was studied in the hypothalamuses of young and aged ovariectomized rats. Hypothalamic tissue was incubated for 60 min in medium containing 3-hydroxybenzylhydrazine dihydrochloride, a dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, and various agents that modify the activity of the PKA pathway. At the end of the incubation, the tissue was homogenized and analyzed for DOPA and TH mass. The in situ molar activity of TH was expressed as the moles of DOPA accumulating in the tissue per mole of TH per hour. Forskolin, an activator of adenylyl cyclase and the cyclic AMP agonist, (Sp)-cyclic adenosine 3',5'-monophosphothioate, significantly (P < .01) increased the in situ molar activity of TH in the hypothalamic dopaminergic (DAergic) neurons of both young and aged rats. Theophylline, a phosphodiesterase inhibitor, did not affect the TH molar activity in the hypothalamuses of aged animals but did significantly (P < .001) increase its activity in those of young rats. When vasoactive intestinal peptide was evaluated, the TH molar activity was significantly (P < .005) increased in the hypothalamuses of young rats but not in those of aged rats. It was suggested that the deficiency of DA secretion by hypothalamic DAergic neurons of aged rats may be the result of insufficient activation of PKA caused by failure of transduction of an extracellular signal to activate adenylyl cyclase and produce cyclic AMP.

Aging↗
PubMed2006

Aging of the rat mesostriatal system: differences between the nigrostriatal and the mesolimbic compartments.

The impairment of the mesostriatal dopaminergic system has been considered responsible for motor and affective disturbances associated with aging and a risk factor for Parkinson's disease. However, the basic mechanisms underlying this phenomenon are still unknown. Here we used biochemical, molecular and morphological techniques directed at detecting flaws in the dopamine synthesis route and signs of dopaminergic degeneration in the rat mesostriatal system during normal aging. We found two different age-related processes. One is characterized by a dopa decarboxylase decrease, and involves both the nigrostriatal and mesolimbic compartments, and is responsible for a moderate dopamine loss in the dorsal striatum, where other parameters of dopamine synthesis are not affected. The other is characterized by axonal degeneration with aggregation of phosphorylated forms of tyrosine hydroxylase (TH) and amyloid precursor protein in degenerate terminals, and alpha-synuclein in their original somata. This process is restricted to mesolimbic regions and is responsible for the decline of TH activity and l-dopa levels and the greater decrease in dopamine levels in this compartment. These findings suggest that both the nigrostriatal and the mesolimbic systems are vulnerable to aging, but in contrast to what occurs in Parkinson's disease, the mesolimbic system is more vulnerable to aging than the nigrostriatal one.

Aging↗
PubMed1978

Microinjection of kainic acid into the rat hippocampus.

The effects of unilateral injection of kainic acid into the rate hippocampus have been examined in terms of morphologic, neurochemical and behavioral sequelae. Infusion of 10 nmoles if kainate causes a rapid and complete degeneration of neuronal perikarya in the entire hippocampal formation followed by gliosis and atrophy of the region. This unilateral neuronal loss is accompanied by a 50% decrease in the specific activity of the biochemical markers for GABAergic neurons including glutamic acid decarboxylase, endogenous GABA and synaptosomal uptake of [3H]GABA. The extrinsic hippocampal cholinergic and noradrenergic afferents also exhibit significant alteration. Although the specific activity of choline acetyltransferase is unaffected and the specific activity of tyrosine hydroxylase is significantly increased in the injected hippocampus, the synaptosomal high affinity uptake process for [3H]choline and [3H]norepinephrine are significantly reduced at 10 days after injection. Whereas the level of endogenous acetylcholine is elevated in the lesioned hippocampus at 2 days after injection, the level of endogenous norepinephrine is reduced. For several hours after intrahippocampal injections of 5 nmoles or more of kainate, rats exhibit epileptiform behavior. Intrahippocampal injection of kainate may be a useful rodent model for temporal lobe seizure disorders.

Animals↗
PubMed2002

Vesicular glutamate transporter DNPI/VGLUT2 mRNA is present in C1 and several other groups of brainstem catecholaminergic neurons.

The mouse glutamate vesicular transporter VGLUT2 has recently been characterized. The rat homolog of VGLUT2, differentiation-associated Na(+)/P(i) cotransporter (DNPI), was examined using a digoxigenin-labeled DNPI/VGLUT2 cRNA probe in the present study to determine which, if any, of the various groups of pontine or medullary monoaminergic neurons express DNPI/VGLUT2 mRNA and, thus, are potentially glutamatergic. DNPI/VGLUT2 mRNA was widely distributed within the brainstem and seemed exclusively neuronal. By using a double in situ hybridization method, the presence of the mRNA for DNPI/VGLUT2 and glutamic acid decarboxylase (GAD)-67 was mutually exclusive. By combining DNPI/VGLUT2 mRNA detection and conventional immunohistochemistry, DNPI/VGLUT2 mRNA was undetectable in lower brainstem cholinergic and serotonergic cells, but it was present in several tyrosine hydroxylase-immunoreactive (TH-ir) cell groups. DNPI/VGLUT2 mRNA was detected in most of the adrenergic neurons of the C1, C2, and C3 groups (75-80% of TH-ir neurons), in the A2 noradrenergic group (80%), and in vast numbers of area postrema cells. Within the A1 region, many fewer TH-ir cells contained DNPI/VGLUT2 (16%). Finally, DNPI/VGLUT2 mRNA was undetectable in the pontine noradrenergic cell groups (A5 and A6/locus coeruleus). In conclusion, the general pattern of DNPI/VGLUT2 expression and its exclusion from GABAergic, cholinergic, and serotonergic neurons supports the notion that DNPI/VGLUT2 mRNA identifies a subset of glutamatergic neurons in the lower brainstem. Within this region several catecholaminergic cell groups appear to be glutamatergic, including but not limited to the adrenergic cell groups C1-C3. Based on the present evidence, the noradrenergic cell groups of the pons (A5 and A6) do not contain either known vesicular glutamate transporter and are most likely not glutamatergic.

Animals↗
PubMed1987

Effects of substrates for aromatic L-amino acid decarboxylase on insulin secretion.

It has been shown that substrates for aromatic L-amino acid decarboxylase potentiate glucose-induced insulin release. Microdissected islets of obese-hyperglycemic mice (Umeå ob/ob) have now been used in a study of the effects of decarboxylase substrates on insulin release induced by secretagogues other than glucose. L-5-hydroxytryptophan (L-5-HTP) at 4 mmol/l potentiated the effect of 1 mumol/l glibenclamide, 20 mmol/l D,L-glyceraldehyde or 20 mmol/l K+, but not that of 50 mumol/l chloromercuribenzene-p-sulphonic acid. The potentiating effect of 4 mmol/l L-5-HTP, 4 mmol/l D,L-m-tyrosine, or 4 mmol/l D,L-o-tyrosine on insulin release induced by 20 mmol/l L-leucine was inhibited by 0.1 mmol/l benserazide. Benserazide did not reduce the effect of 10 mmol/l L-glutamine on L-leucine-induced insulin release. L-dihydroxyphenylalanine inhibited glucose-induced insulin secretion at 0.1 mmol/l with a tendency towards a reduction also at lower concentrations. The findings support the hypothesis that increased activity of aromatic L-amino acid decarboxylase can stimulate islet B cell function.

5-Hydroxytryptophan↗
PubMed1999

Maternal hypothyroxinemia disrupts neurotransmitter metabolic enzymes in developing brain.

Maternal thyroid status influences early brain development and, consequently, cognitive and motor function in humans and rats. The biochemical targets of maternal thyroid hormone (TH) action in fetal brain remain poorly defined. A partially thyroidectomized rat dam model was therefore used to investigate the influence of maternal hypothyroxinemia on the specific activities of cholinergic and monoaminergic neurotransmitter metabolic enzymes in the developing brain. Maternal hypothyroxinemia was associated with reduced monoamine oxidase (MAO) activity in fetal whole brain at 16 and 19 days gestation (dg). A similar trend was observed for choline acetyltransferase (ChAT) activity. In contrast, DOPA decarboxylase (DDC) activity was markedly elevated at 21 dg. Further study of these enzymes at 14 dg showed no differences between normal and experimental progeny - suggesting they become TH sensitive after this age. Tyrosine hydroxylase (TyrH) and acetylcholinesterase (AChE) activities were unaffected prenatally. During postnatal development, the activities of TyrH, MAO, DDC and, to a lesser extent, AChE were increased in a brain region- and age-specific manner in experimental progeny. The prenatal disturbances noted in this study may have wide-ranging consequences since they occur when neurotransmitters have putative neurotropic roles in brain development. Furthermore, the chronic disturbances in enzyme activity observed during postnatal life may affect neurotransmission, thereby contributing to the behavioural dysfunction seen in adult progeny of hypothyroxinemic dams.

Aging↗
PubMed2000

An altered histaminergic innervation of the substantia nigra in Parkinson's disease.

The central histaminergic system is one of the subcortical aminergic projection systems involved in several regulatory functions. The central dopaminergic and histaminergic systems interact extensively, but little is known about the histaminergic system in diseases affecting the dopaminergic neurons. The distribution of histaminergic fibers in the substantia nigra (SN) in postmortem brain samples from patients suffering from Parkinson's disease (PD) and normal controls was examined with a specific immunohistochemical method. Direct connections between dopaminergic neurones and histaminergic fibers were observed. Histamine in human SN was stored in fibers and varicosities. Sites of histamine formation were examined by l-histidine decarboxylase in situ hybridization. In both normal and PD brains HDC mRNA was found only in posterior hypothalamus and not in SN. The presence of histaminergic innervation of the human substantia nigra pars compacta (SNc) and reticulata (SNr), paranigral nucleus, radix of oculomotor nerve, and parabrachial pigmented nucleus was demonstrated. The density of histaminergic fibers in the middle portion of SNc and SNr was increased in brains with PD. In PD the morphology of histaminergic fibers was also altered; they were thinner than in controls and had enlarged varicosities. An increase of histaminergic innervation may reflect a compensatory event due to deficiency of, e.g., dopamine or a putative fiber growth inhibitory factor. Whether the changes seen in histaminergic fibers in PD are primary or secondary remains to be investigated.

Adult↗
PubMed1981

Neurotransmitter-synthesizing enzymes in 14 human neuroblastoma cell lines.

Fourteen human neuroblastoma cell lines were studied for expression and regulation of neurotransmitter-synthesizing enzymes. All cell lines contained activities of adrenergic and/or cholinergic neurons and 13 expressed activities for both. None contained enzymes for serotonergic or GABAergic neurons. Enzyme activity was characteristic for a given cell line. Enzyme activity in cell lines was sensitive to growth phase, culture medium, and concentration of fetal bovine serum.

Aromatic-L-Amino-Acid Decarboxylases↗