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At least 1,009 records · Page 56Linked to original sources
PubMed1994

Immunohistochemical localization of L-dopa and aromatic L-amino acid-decarboxylase in the rat retina.

PURPOSE: The purpose of this study was threefold: to determine if some catecholaminergic amacrine cells of the rat retina use L-DOPA as their neurotransmitter, especially the small (2CA) cells that are immunoreactive to tyrosine hydroxylase but not to dopamine; to understand better the possible existence of serotoninergic cells in the rat retina; and to clarify the role of serotonin in the metabolism of melatonin. METHODS: Immunohistochemistry using antibodies against tyrosine hydroxylase (TH), L-DOPA, aromatic L-amino acid decarboxylase (AADC), dopamine (DA), and tyramine in rat retinal wholemounts, serial sections, and various combinations of double labeling. RESULTS: Paired wholemounts immunoreacted with anti-TH/AADC antibodies did not show a significant difference in densities of TH+ and AADC+ amacrine cells. All the TH+ cells exhibited AADC immunoreactivity. There were no AADC-immunoreactive cells lacking TH. A few TH+ cells exhibited L-DOPA immunoreactivity; they also contained AADC. The inner segments of photoreceptor cells were labeled by the anti-AADC antibody. The antibody to tyramine did not label any cells in the rat retina. CONCLUSIONS: L-DOPA can be excluded as a candidate active substance for the small TH+ amacrine cells that do not exhibit DA-immunoreactivity. The L-DOPA-immunoreactivity restricted to a small number of large TH+ amacrine cells probably does not represent an end product. Tyramine also does not appear to constitute a neurotransmitter in the rat retina. We confirm that there are no serotonin-synthesizing amacrine cells in the rat retina. The localization of AADC-immunoreactivity in the photoreceptor cell inner segments is possibly related to the biosynthetic pathway of melatonin from 5-hydroxytryptophan.

Animals↗
PubMed1980

Antagonism of ethanol's central stimulation by catecholamine receptor agonists.

The effect of ethanol (2 g/kg) on brain catecholamine neurons in the rat as well as its interaction with catecholamine receptor agonists was studied utilizing single unit recording techniques. Identified dopamine (DA) neurons of the zona compacta, substantia nigra as well as noradrenaline (NA) neurons of the locus coeruleus showed no alterations in firing rate at ethanol administration. Also the function of their presynaptic DA and NA receptors, respectively, appeared normal judging from the unaltered inhibitory response to systemically or microiontophoretically applied receptor agonists, apomorphine and clonidine, respectively, when applied in small doses. In contrast, the catecholamine releasing agent amphetamine caused inhibition of firing of the central catecholamine neurons in the same anesthetized preparation. The rate of tryosine hydroxylation in vivo in central DA and NA neurons measured as the amount of Dopa accumulated in various brain regions following inhibition of aromatic l-amino acid decarboxylase by NSD 1015, 150 md/kg i.p., was significantly increased by ethanol in anesthetized rats. Consequently, the present data do not support the hypothesis derived largely from behavioural evidence that ethanol causes inactivation of central DA and NA neurons. The antagonism by catecholamine receptor agonists, apomorphine and clonidine of ethanol's behaviourally stimulant action may thus be of unspecific character. The results indicate that alterations in tyrosine hydroxylase activity, when measured as Dopa formation after decarboxylase inhibition, can occur without concomitantly altered impulse activity in central DA or NA neurons. At present the action of ethanol on brain DA and NA neurons remains unclear and necessitates further studies.

Animals↗
PubMed1980

[Demonstration of neuronal activities in primary cultures from fetal mouse hypothalamus maintained in a serum-free medium].

Fetal neuronal cells dissociated from mouse hypothalamus are able to grow in a serum-free medium for two to four weeks. Several neuronal activities have been measured during the in vitro cell development. Whereas glutamic acid decarboxylase (EC 4.1.1.15) activity disappears, those of thyroliberin (TRH) and tyrosine hydroxylase (EC. 1.14.16.2) remain stable, and acetylcholine transferase one (EC 2.3.1.6) rises earlier than in a serum supplemented medium. These results show that primary cultures grown in serum-free medium offer a promising model for studying neuronal activity differentiation.

Animals↗
PubMed1990

Immunohistochemical analysis of the visual wulst of the pigeon (Columba livia).

The avian wulst, a laminated "bulge" in the dorsal telencephalon, contains several distinct regions. The posterolateral portion (visual wulst) has been proposed to be an avian equivalent of the mammalian striate cortex. The present study examines specific neurotransmitters and neuropeptides within the visual wulst by immunohistochemical techniques. Antisera and monoclonal antibodies against choline acetyltransferase (ChAT), nicotinic acetylcholine receptor (nAChR), tyrosine hydroxylase (TH), serotonin (5-HT), glutamic acid decarboxylase (GAD), gamma-aminobutyric acid A receptor (GABAAR), cholecystokinin (CCK), substance P (SP), leucine-enkephalin (L-ENK), neurotensin (NT), neuropeptide Y (NPY), somatostatin (SRIF), corticotropin-releasing factor (CRF), and vasoactive intestinal polypeptide (VIP) were used. Somata and neuropil displaying specific immunoreactivity were generally distributed in accordance with the laminar cytoarchitectonic organization of the wulst. The superficial layer of the wulst, the hyperstriatum accessorium, contained the highest densities of TH-, 5-HT-, SP-, NPY-, SRIF-, CRF-, and VIP-positive neuropil in the wulst, whereas the highest density of CCK- and NT-staining was found in the deepest layer of the wulst, the hyperstriatum dorsale. In addition to the traditionally defined four laminae of the wulst, the immunoreactive staining revealed several subregions within each lamina. The most dorsolateral portion of the wulst contained the highest densities of ChAT- and L-ENK-stained fibers in the wulst, as well as moderately dense staining of neuropil for 5-HT-, TH-, SP-, and CCK-like immunoreactivity. The nAChR-immunoreactivity was faint and distributed rather uniformly throughout the wulst. The results suggest that the wulst consists of multiple regional variations within layers comparable to laminar variations found within different cytoarchitectonic areas of the mammalian neocortex.

Animals↗
PubMed1998

Dopamine formation from tyramine by CYP2D6.

Dopamine is formed form L-tyrosine by tyrosine hydroxylase and aromatic L-amino acid decarboxylase. In addition to this pathway, however, the formation of catecholamines, including dopamine, from trace amines such as tyramine by hepatic microsomes has been demonstrated. In this study, we investigated the formation of dopamine from trace amines, using human hepatic microsomes and human cytochrome P450 (CYP) isoforms expressed in yeast. Among the 11 isoforms of human CYP expressed in yeast, CYP2D6 was the only isoform exhibiting strong ability to convert p-tyramine and m-tyramine to dopamine. In studies with human hepatic microsomes, the hydroxylation of tyramine to dopamine was inhibited by bufuralol, a typical substrate for CYP2D isoforms, and anti-CYP2D1 antiserum. This is the first report showing that CYP2D is capable of converting tyramine to dopamine. The Km values of CYP2D6, expressed in yeast, for p-tyramine and m-tyramine were 190.1 +/- 19.5 microM and 58.2 +/- 13.8 microM, respectively. Tyramine is an endogenous compound which exists in the brain as a trace amine but is also an exogenous compound which is found in foods such as cheese and wine. Our results suggest that dopamine is formed from endogenous and/or exogenous tyramine by this CYP2D isoform.

Animals↗
PubMed1998

Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene.

To ascertain the function of an orphan nuclear receptor Nurr1, a transcription factor belonging to a large gene family that includes receptors for steroids, retinoids, and thyroid hormone, we generated Nurr1-null mice by homologous recombination. Mice, heterozygous for a single mutated Nurr1 allele, appear normal, whereas mice homozygous for the null allele die within 24 h after birth. Dopamine (DA) was absent in the substantia nigra (SN) and ventral tegmental area (VTA) of Nurr1-null mice, consistent with absent tyrosine hydroxylase (TH), L-aromatic amino acid decarboxylase, and other DA neuron markers. TH immunoreactivity and mRNA expression in hypothalamic, olfactory, and lower brain stem regions were unaffected. L-Dihydroxyphenylalanine treatments, whether given to the pregnant dams or to the newborns, failed to rescue the Nurr1-null mice. We were unable to discern differences between null and wild-type mice in the cellularity, presence of neurons, or axonal projections to the SN and VTA. These findings provide evidence for a new mechanism of DA depletion in vivo and suggest a unique role for Nurr1 in fetal development and/or postnatal survival.

Animals↗
PubMed1979

Growth regulation by nerve growth factor.

Although a great deal of descriptive information has been obtained about the actions of nerve growth factor on its target tissues, its structure, its receptors, and even its biosynthesis, there is no clear understanding, as yet, of the intracellular events mediating its transcriptional involvements. Work in this laboratory over the past five years has uncovered a number of nerve growth factor-initiated intracellular changes in sympathetic neurons and other nerve growth factor-sensitive systems, and has provided a framework into which they might fit. This article is written in an attempt to collect the data in a single communication and to suggest at least one mechanism by which the nerve growth factor may work.

Animals↗
PubMed1979

The involvement of serotonergic neurons in the central nervous system as the possible mechanism for slow head-shaking behavior induced by methamphetamine in rats.

Following the IV administration of d-methamphetamine (MA), rats showed slow head shaking (SHS) and stereotyped gnawing (SG) behaviors in a dose-dependent manner. Methysergide, cyrpoheptadine, and p-chlorophenylalanine given intracerebroventricularly (ICV) or systemically significantly blocked SHS behavior induced by 10 mg/kg MA. Combined administration of L-5-hydroxytryptophan and peripheral decarboxylase inhibitor (Ro 4-4602) enhanced SHS behavior. Tyrosine hydroxylase inhibitor (H44/68) blocked SG behaviors, but dopamine-beta-hydroxylase inhibitors (FLA 63 and U-14, 624) and combined administration of L-3,4-dihydroxyphenylalanine and Ro-4-4602 enhanced it. These drugs did not affect SHS behavior. Phentolamine, phenoxybenzamine, clonidine, isoproterenol, and propranolol given ICV or systemically showed no effect on either SHS or SG behaviors. These results suggest that SHS behavior is produced by the activation of seronergic neurons in the central nervous system and are consistent with the view that SG behaviors are mediated through the release of dopamine. Some neuroleptics inhibited SHS as well as SG behaviors, but the older of inhibitory activity of neuroleptics onSHS behavior was quite different from their effects on SG behaviors induced by MA or apomorphine.

Animals↗
PubMed1990

High-performance liquid chromatographic analysis of monoamines and some of their gamma-glutamyl conjugates produced by the brain and other tissues of Helix aspersa (Gastropoda).

1. Earlier reports from this and other laboratories have indicated that wide variations exist in estimates of the concentrations of norepinephrine in the brain and heart of the snail Helix aspersa. This is a report on investigations of norepinephrine concentrations in Helix aspersa tissues using high-performance liquid chromatography with electrochemical detection. In addition, the effects of treatment with some amino acid precursors or enzyme inhibitors on the concentrations of norepinephrine, dopamine, 5-hydroxytryptamine, and some of their metabolites were investigated. 2. The levels of norepinephrine in the brain were low (46 ng/g) in comparison to dopamine (2.1) micrograms/g) and 5-hydroxytryptamine (2.6 micrograms/g). Epinephrine was not observed in either snail heart of snail nervous tissue. 3. Administration of L-3,4-dihydroxyphenylalanine resulted in elevated snail brain dopamine, while 3,4-dihydroxyphenylserine treatment increased norepinephrine. Treatment with blockers of tyrosine hydroxylase and aromatic-L-amino acid decarboxylase reduced dopamine concentrations without affecting 5-hydroxytryptamine. 4. The dopamine metabolite 3,4-dihydroxyphenylacetic acid was observed only after administration of L-3,4-dihydroxyphenylalanine or dopamine and then only in very small amounts. At no time was the dopamine metabolite homovanillic acid or the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid observed in brain, heart, or whole-body extracts of the snail. 5. Incubation of nervous tissue with either dopamine or 5-hydroxytryptamine resulted in the production of electrochemically active metabolites which were identified by oxidation characteristics and cochromatography with synthesized standards as the gamma-glutamyl conjugates of the amines. Treatment of snails with 5-hydroxytryptamine or dopamine also resulted in the production of gamma-glutamyl conjugates. 6. The present experiments show that great care must be exercised when measuring monoamines and their metabolites in gastropod tissues by high-performance liquid chromatography with electrochemical detection.

Animals↗
PubMed1988

Biochemical evidence for presence of dopamine beta-hydroxylase in rat retina.

Previously, we demonstrated immunocytochemically that certain phenylethanolamine N-methyltransferase neurons in the inner nuclear layer of rat retina contain other catecholamine synthesizing enzymes, including tyrosine hydroxylase and aromatic-L-amino acid decarboxylase but not dopamine beta-hydroxylase (DBH), the norepinephrine biosynthetic enzyme. In the present study by using a sensitive radioenzymatic assay for DBH we demonstrated the presence of DBH enzymatic activity in retinal extracts. Immunocytochemical studies, however, failed to demonstrate DBH-immunoreactive perikarya even in animals pretreated with colchicine, an inhibitor of axonal transport. Probably causes for these discrepant findings are discussed.

Animals↗
PubMed1994

Immunohistochemical studies on the intestinal nerve of Remak in the male chicken.

A peroxidase anti-peroxidase method was used to investigate and compare the distribution of neuropeptide and catecholamine synthesizing enzyme immunoreactive (IR) ganglion cells and nerve fibres in the intestinal nerve of Remak (INR) of male chickens. In the INR there were three kinds of ganglion cells: tyrosine hydroxylase (TH)-, aromatic L-amino acid decarboxylase (AADC)- and phenylethanolamine-N-methyltransferase (PNMT)-IR cells; AADC- and PNMT-IR but TH-immunonegative cells; and ganglion cells being immunoreactive for methionine enkephalin (mENK)- and somatostatin (SOM). The first one was distributed throughout the INR. The second was restricted in the ileojejunal region, and the last was localized in the rectal region. Substance P- and vasoactive intestinal polypeptide-IR nerve fibres were distributed in common but variable in number around three kinds of ganglion cells. Then TH-IR cells were characterized by the distribution of many calcitonin gene related peptide- and a few cholecystokinin-IR fibres. mENK and SOM-IR cells, and TH-immunonegative cells were distinguished by the distribution of SOM- and galanin-IR fibres. In addition, TH-immunonegative cells were characterized by the distribution of mENK- and neuropeptide Y-IR nerve fibres which were very few in number. Fig. 21 summarizes the connections described in the present study.

Animals↗
PubMed2004

Localization of Mel1b melatonin receptor-like immunoreactivity in ocular tissues of Xenopus laevis.

The circadian signaling molecule, melatonin, is produced by pinealocytes and retinal photoreceptors. In the retina, melatonin is thought to diffuse into the inner retina to act as a paracrine signal of darkness by binding to specific receptors in retinal neurons. The retinal cell locations of the Mel1a and Mel1c melatonin receptor types have been reported, but the localization of the Mel1b receptor, which is the most highly expressed melatonin receptor type in the retina, is unknown. To determine the cellular distribution of Mel1b melatonin receptor protein in the Xenopus laevis retina and other ocular tissues, polyclonal antibodies were raised against a peptide fragment of the X. laevis Mel1b receptor. Western blot analysis of several ocular tissues revealed the presence of one or more immunoreactive bands in the sclera, cornea, lens, retinal pigment epithelium (RPE)/choroid, and neural retina. In the neural retina, the major immunoreactive bands displayed electrophoretic mobilities corresponding to approximately 35, 42, 45, and 80 Kd. Sections of X. laevis eyes were analyzed by immunocytochemistry and confocal microscopy, in combination with antibodies against the Mel1a melatonin receptor, a rod photoreceptor-specific protein, opsin, and two amacrine cell-specific markers, tyrosine hydroxylase (TOH; dopaminergic cells) and glutamic acid decarboxylase (GAD; GABA-ergic cells). Mel1b immunoreactivity was localized to the apical membranes of RPE cells, and punctate Mel1b immunoreactivity was observed in both rod and cone photoreceptor inner segments. Presumptive horizontal cells that ramify in the outer plexiform layer (OPL) were immunoreactive for Mel1b, and were exclusive of the Mel1a immunoreactivity present in the OPL. Neither TOH nor GAD co-localized with the Mel1b immunoreactivity that was present in the inner plexiform layer (IPL), suggesting that Mel1b is not expressed in dopaminergic or GABA-ergic amacrine cells. Mel1b immunoreactivity was observed in ganglion cells of the retina, a population of cells covering the outer surface of the outer fibrous layer of the sclera, and in lens fibers located in the outer regions of the lens. These results suggest that melatonin may influence retinal function by binding to receptors on RPE and photoreceptor cells, and by acting on neurons of the inner retina that do not use dopamine or GABA as a neurotransmitter. Furthermore, melatonin may bind to receptors on cells located in the sclera and lens, perhaps to modify the growth or function of these ocular tissues.

Animals↗
PubMed2002

Enhanced expression of GTP cyclohydrolase I in V-1-overexpressing PC12D cells.

Three of the catecholamine-synthesizing enzymes, i.e., tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase, and dopamine beta-hydroxylase, were earlier shown to be up-regulated in cloned PC12D cells overexpressing V-1, a cdc10/SWI6 motif-containing protein. GTP cyclohydrolase I (GCH) is the rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin (BH(4)), known as an essential cofactor for TH; and here we found the increased expression of GCH in V-1-overexpressing clones. Both GCH activity and total biopterin content were highly increased in the V-1 clones; whereas the activity of sepiapterin reductase, enzyme in the final step of the BH(4) biosynthesis, was not altered. Biochemical analyses revealed increased levels of GCH protein, mRNA, and transcription in the V-1 clones. Promoter analysis showed increased reporter activity in the construct with 150 bp of the promoter region of the human GCH gene, suggesting the involvement of cAMP-responsive element-mediated transcriptional regulation.

Animals↗
PubMed2001

Differential expression of the noradrenaline transporter in adrenergic chromaffin cells, ganglion cells and nerve fibres of the rat adrenal medulla.

Expression of the noradrenaline transporter (NAT) was identified in various cell and fibre populations of the rat adrenal medulla, examined with immunohistochemistry and confocal microscopy. Immunoreactivity for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), aromatic-L-amino-acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) was present in all chromaffin cells, while phenylethanolamine N-methyltransferase (PNMT) was used to determine adrenergic chromaffin cell groups. Labelling with NAT antibody was predominantly cytoplasmic and colocalised with PNMT immunoreactivity. Noradrenergic chromaffin cells were not NAT immunoreactive. Additionally, NAT antibody labelling demonstrated clusters of ganglion cells (presumably Type I) and nerve fibres. Expression of TH, AADC, DBH, PNMT and NAT mRNA was examined using reverse transcription-polymerase chain reaction (RT-PCR) from adrenal medulla punches and single chromaffin cells, and results were consistent with those obtained with immunocytochemistry. Chromaffin cells and fibres labelled with antibodies against growth associated protein-43 (GAP-43) were not NAT immunoreactive, while ganglion cells were doubled labelled with the two antibodies. The presence of NAT in adrenergic chromaffin cells, and its absence from noradrenergic cells, suggests that the adrenergic cell type is primarily responsible for uptake of catecholamines in the adrenal medulla.

Adrenal Medulla↗
PubMed1992

Ornithine decarboxylase activity is critical for cell transformation.

The enzyme ornithine decarboxylase is the key regulator of the synthesis of polyamines which are essential for cell proliferation. Expression of this enzyme is transiently increased upon stimulation by growth factors, but becomes constitutively activated during cell transformation induced by carcinogens, viruses or oncogenes. To test whether ornithine decarboxylase could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 cells with expression vectors carrying the complementary DNA encoding human ornithine decarboxylase in sense and antisense orientations. The increased expression of the enzyme (50-100-times endogenous levels) induced not only cell transformation, but also anchorage-independent growth in soft agar and increased tyrosine phosphorylation of a protein of M(r) 130K. Expression of ornithine decarboxylase antisense RNA was associated with an epithelioid morphology and reduced cell proliferation. Moreover, blocking the endogenous enzyme using specific inhibitor or synthesizing antisense RNA prevented transformation of rat fibroblasts by temperature-sensitive v-src oncogene. Our results imply that the gene encoding ornithine decarboxylase is a proto-oncogene central for regulation of cell growth and transformation.

3T3 Cells↗
PubMed1998

Involvement of Myc targets in c-myc and N-myc induced human tumors.

The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of c-Myc target genes in human oncogenesis induced by c-myc or N-myc. In MCF-7 breast cancer cells, the induction of c-myc expression by estrogen was followed by the induction of all the Myc targets that we examined, indicating that those genes can serve as c-Myc targets in human oncogenesis. Moreover, in breast tumors exhibiting c-myc overexpression, several Myc targets were also overexpressed. A clear correlation between the expression of c-myc and its targets was also detected in Burkitt's lymphomas, which involve a specific translocation of c-myc gene, but not in other lymphoma cells. Yet, in cells derived from a neuronal origin the pattern of expression of Myc targets was more complex. In a neuroepithelioma cell line that overexpresses c-myc, only some targets were expressed. In addition in neuroblastomas, in which N-myc is amplified and overexpressed, only ODC was overexpressed in all cell lines, while all other target genes were expressed in only some of the cell lines. The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identified originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell specific factors are also needed for transcription of the target genes.

Breast Neoplasms↗