UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of cells exhibiting leucine-enkephalin-, substance P- and glutamate decarboxylase-like immunoreactivity was demonstrated in dissociated cultures from newborn rat neostriatum. The size and shape of the enkephalin-immunoreactive cells varied, but they were generally larger than substance P- and glutamate decarboxylase-immunoreactive cells, which formed relatively uniform cell populations. Cells of apparently non-neuronal origin did not show any immunoreactivity. It is unlikely that enkephalin is present in the same cells that contain substance P or glutamate decarboxylase because of morphological differences between these cells. The possible coexistence of substance P and glutamate decarboxylase in the same cells however, could not be excluded. The results of this study confirm that the cell bodies of neurons containing three possible neurotransmitters are located in the neostriatum.
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PMID:Demonstration of enkephalin-, substance P- and glutamate decarboxylase-like immunoreactivity in cultured cells derived from newborn rat neostriatum. 616 8

Chronic neuroleptic treatment in rat produces vacuous chewing movements (VCMs), analogous to TD in humans. We hypothesized that these hyperkinetic movements were due to alterations in striatonigral and striatopallidal GABAergic spiny II neurons. Rats were treated for 36 weeks with haloperidol decanoate and withdrawn for 28 weeks. Striatonigral and striatopallidal neurons were assessed using in situ hybridization histochemistry for mRNA levels of D1 and D2 dopamine receptors, preproenkephalin (ENK), prodynorphin (DYN), protachykinin (substance P), and glutamate decarboxylase (GAD67) in the dorsolateral and ventromedial striatum as well as the nucleus accumbens. Rats that did not develop VCMs (-VCM) had increased D2 receptor and DYN mRNA, and reduced substance P mRNA in the dorsolateral striatum. Rats with persistent VCMs (+VCM) had increased D2 receptor, ENK, and DYN mRNA in both striatal regions, and increased ENK and DYN mRNA in the nucleus accumbens, compared with controls. Relative to -VCM rats, however, +VCM rats only had increased ENK mRNA in the nucleus accumbens. Considering the overall pattern of mRNA changes, the data suggest that alterations in both the D1-mediated striatonigral and the D2-mediated striatopallidal pathways play a role in the expression of the VCM syndrome. To the extent that gene expression parallels changes in neuronal activity, this implies that the VCM syndrome is associated with increased activity in both pathways.
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PMID:Alterations in mRNA levels of D2 receptors and neuropeptides in striatonigral and striatopallidal neurons of rats with neuroleptic-induced dyskinesias. 753 73

Disruption of dopaminergic neurotransmission in the striatum by neurotoxic lesions of the substantia nigra leads to increases in glutamic acid decarboxylase and proenkephalin messenger RNA expression, and to decreases in preprotackykinin (the precursor molecule for substance P) messenger RNA expression in the two populations of striatal medium-sized spiny projection neurons. These cells also express TrkB, the neurotrophin receptor for brain-derived neurotrophic factor and neurotrophin 4/5, and TrkC, the receptor for neurotrophin-3. Since there is some indication that exogenous brain-derived neurotrophic factor can exert neuromodulatory effects in the basal ganglia, we studied the effects of repeated intrastriatal injections of the four members of the neurotrophin family of neural growth factors, nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 on the expression of striatal neurotransmitter-related genes in the unilaterally 6-hydroxydopamine-lesioned rat using in situ hybridization histochemistry. We found that 4 micrograms/day of brain-derived neurotrophic factor or neurotrophin-4/5 when injected intrastriatally for eight consecutive days led to a normalization of the denervation-induced decrease of preprotachykinin messenger RNA when compared to animals injected with equivalent doses of nerve growth factor, neurotrophin-3, or vehicle. Neurotrophin-4/5 alone also normalized expression of messenger RNA encoding the 67 x 10(3) mol. wt isoform of glutamate decarboxylase, while none of the neurotrophins had a significant effect on preproenkephalin messenger RNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum. 761 69

The effect of a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle in rats and subsequent L-DOPA treatment for eight weeks on preproenkephalin, preprotachykinin and glutamate decarboxylase (M(r) 67,000) gene expression in the striatum was investigated by in situ hybridization. A 6-hydroxydopamine lesion of the medial forebrain bundle markedly increased the level of preproenkephalin messenger RNA (+66%) and modestly elevated the level of glutamate decarboxylase (M(r) 67,000) messenger RNA (+36%) in the denervated striatum, but caused a decrease in the level of preprotachykinin messenger RNA (-54%) relative to the intact striatum and to sham-lesioned control animals. Treatment with L-DOPA (200 mg/kg/24 h) for eight weeks reduced but did not abolish the 6-hydroxydopamine lesion-induced elevation of preproenkephalin messenger RNA and slightly reduced the elevation of glutamate decarboxylase (M(r) 67,000) messenger RNA in denervated striatum relative to intact side and control groups. However, L-DOPA treatment almost completely reversed the decrease in preprotachykinin messenger RNA caused by 6-hydroxydopamine lesioning when compared to intact side and control groups. The effect of L-DOPA on the gene expression of preproenkephalin and glutamate decarboxylase (M(r) 67,000) differs from the increase in striatal enkephalin content and glutamate decarboxylase activity previously found following L-DOPA treatment. In contrast, L-DOPA reversed the changes in preprotachykinin messenger RNA, reflecting previously reported increases in substance P content. The findings provide new evidence that chronic L-DOPA treatment differentially affects direct striatonigral and indirect striatopallidal pathways at the molecular level.
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PMID:Chronic L-DOPA treatment differentially regulates gene expression of glutamate decarboxylase, preproenkephalin and preprotachykinin in the striatum of 6-hydroxydopamine-lesioned rat. 763 69

In the present study, we have re-examined the heterogeneous nature of intrastriatal striatal transplants derived from embryonic day 14-15 rat striatal primordia implanted into the previously excitotoxically lesioned striatum of adult rats, using in situ hybridization histochemistry to localize neurotransmitter-related messenger RNAs. These grafts are characterized by discrete patches of DARPP-32 messenger RNA expression, which cover approximately one-third of the cross-sectional graft area. The messenger RNAs encoding for preproenkephalin (the enkephalin precursor), preprotachykinin (precursor to substance P), choline acetyltransferase, as well as the D1 and D2 dopamine receptors, which are abundant in the normal striatum, were all present in the striatal grafts and were expressed almost exclusively in the DARPP-32-positive graft regions. In these graft regions, the expression of the neurotransmitter-related messenger RNAs was generally similar to that seen in the intact striatum, although the level of expression of preproenkephalin and preprotachykinin messenger RNAs varied notably among the patches of expression. Cellular analysis performed on individual patches showed that the expression per cell of preproenkephalin and preprotachykinin messenger RNAs was inversely related, such that patches with higher than normal preproenkephalin messenger RNA levels displayed lower than normal preprotachykinin messenger RNA levels, and vice versa. Moreover, messenger RNA expression for the dopamine D2 receptor was overall lower than that for the dopamine D1 receptor, both with respect to the level per cell and the number of positive cells within the DARPP-32 patches. Glutamate decarboxylase messenger RNA was expressed throughout the grafts, in 98% of all neurons located in the DARPP-32-positive regions and in 75% of all neurons in the non-DARPP-32 regions of the graft. Interestingly, the cellular expression of glutamate decarboxylase messenger RNA was considerably higher in the non-DARPP-32 expressing regions than that in the DARPP-32 messenger RNA-rich areas, where it approximated that of the intact striatum. Furthermore, grafted neurons located outside the DARPP-32-expressing regions displayed similar levels of expression to those found in the overlying cortex and in the closely adjacent globus pallidus. To further characterize the DARPP and non-DARPP graft compartments, messenger RNAs encoding the alpha 1 and beta 2 subunits of the GABAA receptor were studied. These receptor subunits, which exhibit a high expression in the host cortex and pallidum but little in the intact striatum, were found in discrete patches situated outside, but often closely associated with, the DARPP-32-rich areas of the graft.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitter-related gene expression in intrastriatal striatal transplants--I. Phenotypical characterization of striatal and non-striatal graft regions. 770 3

The phenotypic characteristics of identified graft neurons in intrastriatal striatal transplants which give rise to efferent projections innervating the host brain were examined using a combination of in situ hybridization histochemistry and fluorescent retrograde tracing. Cell suspension grafts of embryonic day 14-15 rat striatal primordia (including both the medial and lateral ganglionic eminences) were implanted into the previously excitotoxically lesioned striatum of adult rats, and after longer than one year the retrograde tracer Fluoro-Gold was injected bilaterally into either the globus pallidus or the substantia nigra. Injections into the globus pallidus resulted in significant retrograde labelling of graft neurons within most of the experimental animals, whereas very few graft cells were labelled after the nigral injections. The vast majority of the neurons retrogradely labelled from the globus pallidus occurred in clusters or patches in the caudal half of the transplants, which corresponded well with DARPP-32 messenger RNA expressing (i.e. striatal) regions of the grafts. Indeed, within these Fluoro-Gold-labelled graft patches, the proportion of retrogradely labelled cells found to contain DARPP-32 messenger RNA was identical to that observed in the intact striatum after similar pallidal injections (93%). In addition, some Fluoro-Gold-labelled cells were found scattered outside the DARPP-32-positive cell clusters; these cells were overall larger and rarely (c. 9%) DARPP-32 messenger RNA-positive. Messenger RNA encoding for glutamate decarboxylase (which was found in 95% of Fluoro-Gold-labelled neurons in the intact striatum) was detected in almost all retrogradely labelled graft neurons located in both the DARPP-32-positive patches of retrograde labelling (93%) and in the DARPP-32-negative regions (82%). In the intact striatum, neurons labelled after pallidal injections of Fluoro-Gold were observed to express preproenkephalin messenger RNA to a greater extent than preprotachykinin messenger RNA (81% vs 21%). Conversely, within the grafts, retrogradely labelled neurons in the patches of Fluoro-Gold-labelled cells were more often found to contain preprotachykinin messenger RNA (50%) than preproenkephalin messenger RNA (21%). The Fluoro-Gold-labelled cells scattered outside the patches of retrograde labelling rarely expressed either preproenkephalin or preprotachykinin messenger RNA. Fluoro-Gold injections into the host substantia nigra resulted in very few retrogradely labelled graft neurons; however, many (85%) of these cells were observed to express glutamate decarboxylase messenger RNA, while only rarely were they observed to contain either DARPP-32, preproenkephalin or preprotachykinin messenger RNAs (c. 10%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurotransmitter-related gene expression in intrastriatal striatal transplants--II. Characterization of efferent projecting graft neurons. 770 12

Patterns of co-localization of serotonin with glutamate decarboxylase (the synthetic enzyme for GABA) or each one of eight neuropeptides (calcitonin gene-related peptide, dynorphin, enkephalin, galanin, neuropeptide Y, neurotensin, substance P and somatostatin) were investigated with dual-colour confocal laser scanning microscopy in the lumbar spinal cords of three adult rats. Four regions of the gray matter were studied (laminae I-II, V, IX and X). The extent of co-localization was estimated by direct assessment of merged pairs of optical sections and by automated image analysis. Co-localization of serotonin and glutamate decarboxylase was found only in a few axons of laminae I-II but was not detected in other laminae. Peptides were not co-localized with serotonin in the superficial dorsal horn but considerable co-localization was found in motor nuclei and sparse co-localization was found in laminae V and X. Galanin and substance P frequently co-existed with serotonin in lamina IX but some co-localization with dynorphin, somatostatin, [Met]enkephalin and neuropeptide Y was also detected. Galanin, substance P and dynorphin were also co-localized with serotonin in a few axons of the deep dorsal horn and in the gray matter around the central canal. Neurotensin and calcitonin gene-related compound did not co-exist with serotonin in any of the laminae investigated. This evidence suggests that different populations of serotoninergic axons project to different regions of the spinal gray matter. Those containing glutamate decarboxylase terminate in the superficial dorsal horn and are likely to be involved in antinociception, whereas those containing peptides terminate principally in motor nuclei and are likely to modulate motor activity.
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PMID:A confocal microscopic survey of serotoninergic axons in the lumbar spinal cord of the rat: co-localization with glutamate decarboxylase and neuropeptides. 893 Oct 11

This study examined the effects of chronic intrastriatal infusion of L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a selective competitive inhibitor of high affinity glutamate transport systems, via osmotic minipumps in rats. Injection of PDC at the rate of 25 nmol/h for 14 days caused striatal lesion. Histological evaluation on frontal striatal sections showed that the lesion was circumscribed to a circular area showing a dramatic neuronal loss accompanied by gliosis and representing 30% of the whole striatal surface at the level of the injection site. A total loss of neurons expressing glutamate decarboxylase (GAD67), enkephalin or substance P mRNA was observed on a similar circular area, suggesting degeneration of the two populations of striatal efferent neurons. In the whole striatum outside the region devoided of hybridization signal, a selective 27% decrease in enkephalin mRNA expression occurred, suggesting a higher sensitivity of enkephalin neurons versus substance P neurons to glutamate uptake-mediated alterations. Injection of PDC at the rate of 25 nmol/h for 3 days produced striatal lesion of similar extent. In contrast, PDC at the rate of 5 nmol/h did not produce neuronal damage when administered over 14 days. This study provides new in vivo evidence that defective glutamate transport is one of the critical conditions that may give rise to toxicity of an endogenous transmitter system in the striatum, and may underlie neuronal death in neurodegenerative diseases.
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PMID:Continuous administration of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate produces striatal lesion. 940 33

To determine whether growth factors of the neurotrophin family are able to regulate the phenotype of striatal projection neurons, cell lines overexpressing brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4/5 were intrastriatally grafted. Striatal projection neurons were examined for the regulation of their soma areas and for the expression of glutamate decarboxylase 67, preprotachykinin A, preproenkephalin and prodynorphin messenger RNAs by in situ hybridization. Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulated the soma area of projection neurons at different distances from the graft, but did not modify their messenger RNA levels. Neurotrophin-3 induced an increase in the soma area of preproenkephalin- and preprotachykinin A-positive neurons, brain-derived neurotrophic factor increased the soma area of only preprotachykinin A-positive neurons, while neurotrophin-4/5 did not produce any effect. Because atrophy and neuronal loss are hallmarks of Huntington's disease, we next examined whether neurotrophins prevent degenerative changes in a quinolinate model of Huntington's disease. Seven days after intrastriatal quinolinate injection, we observed a halo of cell loss around the injection sites, reduced soma area of glutamate decarboxylase 67-, preproenkephalin- and preprotachykinin A-positive neurons bordering the lesion, and a decrease in the messenger RNA levels of glutamate decarboxylase 67 and these neuropeptides. Grafting of cell lines expressing brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4/5 reduced the size of the lesion for preproenkephalin-, preprotachykinin- and glutamate decarboxylase 67-, but not for prodynorphin-positive neurons. Moreover, the three neurotrophins prevented the atrophy of all projection neurons, and the lesion-induced decrease in preproenkephalin and preprotachykinin A messenger RNA levels. We conclude that neurotrophins differentially regulate the phenotype of striatal projection neurons and prevent degenerative changes. The higher efficiency of neurotrophin-3 suggests a potential therapeutic application of this molecule in neurological disorders affecting striatal projection neurons, such as Huntington's disease.
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PMID:Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulate the phenotype and prevent degenerative changes in striatal projection neurons after excitotoxicity in vivo. 1039 33

The expression of 34 transmitter-related genes has been examined in the cholinergic neurones of rat striatal brain slices, with the aim of correlating gene expression with functional activity. The mRNAs encoding types I, II/IIA, and III alpha subunits of the voltage-sensitive sodium channels were detected, suggesting the presence of these three types of sodium channel. Similarly, mRNAs encoding all four alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-type glutamate receptor subunits and the NR1 and NR2A, 2B, and 2D subunits of the NMDA-type glutamate receptors were detected, suggesting that various combinations of these subunits mediate the cellular response to synaptically released glutamate. Other mRNAs detected included the NK1 and NK3 tachykinin receptors, all four known adenosine receptors, and the GABA-synthesising enzyme glutamate decarboxylase. Subpopulations of these cholinergic neurones have been identified on the basis of the expression of the NK3 tachykinin receptor in 5% and the trkC neurotrophin receptor in 12% of the cells investigated.
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PMID:Correlating physiology with gene expression in striatal cholinergic neurones. 1064 37

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