Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular and subcellular distributions of the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring glutamate receptor (GluR) in monkey striatum were demonstrated immunocytochemically using anti-peptide antibodies to individual subunits of the AMPA receptor. These antibodies specifically recognize GluR1, GluR4, and an epitope common to GluR2 and GluR3 (designated as GluR2/3). On immunoblots, the antibodies detect proteins ranging from 102 to 108 kDa in total homogenates of monkey striatum, hippocampus, and cerebellum. By immunoblotting, GluR1 and GluR2/3 are considerably more abundant than GluR4 in the caudate nucleus. Within the caudate nucleus, putamen, and nucleus accumbens, numerous neuronal perikarya, dendrites, and spines show GluR1 and GluR2/3 immunoreactivities. GluR1- and GluR2/3-enriched striatal neurons have the morphology, transmitter specificity, and distribution of medium-sized (10-20 microns) spiny neurons; large (20-60 microns) round neurons exhibit GluR4 immunoreactivity. GluR1 immunoreactivity, but not GluR2/3 or GluR4 immunoreactivity, is more intense in the ventral striatum (i.e., nucleus accumbens) than in the dorsal striatum, and GluR1 is enriched within dendritic spines in the neuropil of the nucleus accumbens and striosomes in the dorsal striatum. In the caudate nucleus, these patches of dense GluR1 immunoreactivity align with regions low in calcium binding protein immunoreactivity and high in substance P immunoreactivity. Within striosomes, GluR1 immunoreactivity is more abundant than GluR2/3 immunoreactivity; GluR4 immunoreactivity is sparse in striosomes, but the matrix contains large, GluR4-positive cholinergic neurons. This study demonstrates that, within monkey striatum, subunits of ionotropic AMPA GluR have differential distributions within striosomes and matrix. Furthermore, the results suggest that neurons within striatal striosomes and matrix may express different combinations of GluR subunits, thus forming receptors with different channel properties and having consequences that may be relevant physiologically and pathophysiologically. Neurons within these two striatal compartments may have different roles in the synaptic plasticity of motor systems.
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PMID:The striatal mosaic in primates: striosomes and matrix are differentially enriched in ionotropic glutamate receptor subunits. 767 61

Glutamate receptors are composed of subtype-specific subunits. Variation in the precise subunit composition of a receptor may result in significant functional differences. Thus, a precise knowledge of subunit composition on striatal neurons is a prerequisite for understanding the selective vulnerability of striatal neurons to excitatory amino acids. In the present study, we used an immunohistochemical double-labelling approach to localize ionotropic glutamate receptor subunits (NMDAR1, GluR1, GluR2/3, GluR4 and GluR5/6/7) on specific striatal neuron populations. Our results showed that striatal cholinergic and somatostatin interneurons were not labelled for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate, receptor subunits GluR1, GluR2/3 and GluR4. Most cholinergic and somatostatin interneurons (83.3% to 100%), however, were double-labelled for the N-methyl-D-aspartate receptor subunit NR1 and kainic acid receptor subunits GluR5/6/7. All parvalbumin interneurons were labelled for GluR1 and GluR4, and 96% GluR1 positive and 95% GluR4 positive neurons were also double-labelled as parvalbumin interneurons. About half of all parvalbumin interneurons co-localized with GluR2/3, and over 97% were labelled for NR1 and GluR5/6/7. Among striatal projection neurons, enkephalin-positive (mainly striatopallidal) neurons, striatonigral neurons (mainly substance P-positive) and calbindin-positive matrix neurons were not immunostained for GluR1 or GluR4. In contrast, 95% to 100% of each of these types of projection neurons were double-labelled for NR1, GluR2/3 and GluR5/6/7. Our results demonstrate that striatal neuron types differ in their expression of ionotropic glutamate receptor subunits and subtypes. The clear difference between striatal interneurons and projection neurons in ionotropic glutamate receptor subtypes/subunits supports the idea that differential glutamate receptor expression mechanism may account for the selective vulnerability of striatal projection neurons to excitotoxicity, and that glutamate receptor-mediated excitotoxicity may be involved in the striatal neurodegenerative diseases.
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PMID:Cellular expression of ionotropic glutamate receptor subunits on specific striatal neuron types and its implication for striatal vulnerability in glutamate receptor-mediated excitotoxicity. 880 93

The mechanisms by which glutamate shapes the activity of striatal medium spiny neurons are of fundamental importance to our understanding of normative and pathological striatal physiology. Non-N-Methyl-D-aspartate (non-NMDA) glutamate receptor expression and function were studied in medium spiny neurons with a combination of single cell RT-PCR, immunocytochemistry and whole-cell voltage-clamp techniques. Reverse transcription polymerase chain reaction analysis found that GluR2 mRNA appeared to be the most abundant and widely distributed AMPA receptor mRNA. GluR1 was also commonly detected. However, GluR3 mRNA was preferentially expressed by neurons coexpressing substance P and enkephalin and GluR4 mRNA was not detected in identified medium spiny neurons. All neuronal classes appeared to express GluR5 or GluR6 and/or GluR7 mRNA in addition to kainate (KA) subunit mRNA. Immunocytochemical studies confirmed the mRNA distributions and also revealed that GluR1 protein was largely restricted to dendritic spines. Although the mRNA and protein for both alpha-amino-3-hydroxy-5-methyl-ioxyzole-4-proprionic acid (AMPA) and KA class subunits was detected, the physiological response to glutamatergic ligands and the benzothiadizine cyclothiazide was characteristic of AMPA, not KA receptors. The AMPA receptor antagonist GYKI 52466 blocked the response to AMPA and all but a small transient component of the response to KA. The current-voltage relationship of the AMPA-evoked currents was relatively linear but Ca2+ fluorometry revealed that substantial changes in intracellular Ca2+ concentration accompanied exposure to either agonist. These results argue that somatodendritic non-NMDA glutamate receptors in medium spiny neurons are primarily GluR2-containing receptors of the AMPA class but that activation of these receptors as a group nevertheless results in a significant Ca2+ influx.
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PMID:Physiological and molecular properties of AMPA/Kainate receptors expressed by striatal medium spiny neurons. 969 Nov 98

This paper reviews the major anatomical and chemical features of the various types of interneurons in the human striatum, as detected by immunostaining procedures applied to postmortem tissue from normal individuals and patients with Huntington's disease (HD). The human striatum harbors a highly pleomorphic population of aspiny interneurons that stain for either a calcium-binding protein (calretinin, parvalbumin or calbindin D-28k), choline acetyltransferase (ChAT) or NADPH-diaphorase, or various combinations thereof. Neurons that express calretinin (CR), including multitudinous medium and a smaller number of large neurons, are by far the most abundant interneurons in the human striatum. The medium CR+ neurons do not colocalize with any of the known chemical markers of striatal neurons, except perhaps GABA, and are selectively spared in HD. Most large CR+ interneurons display ChAT immunoreactivity and also express substance P receptors. The medium and large CR+ neurons are enriched with glutamate receptor subunit GluR2 and GluR4, respectively. This difference in AMPA GluR subunit expression may account for the relative resistance of medium CR+ neurons to glutamate-mediated excitotoxicity that may be involved in HD. The various striatal chemical markers display a highly heterogeneous distribution pattern in human. In addition to the classic striosomes/matrix compartmentalization, the striosomal compartment itself is composed of a core and a peripheral region, each subdivided by distinct subsets of striatal interneurons. A proper knowledge of all these features that appear unique to humans should greatly help our understanding of the organization of the human striatum in both health and disease states.
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PMID:Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington's disease. 1108 88

Previous evidence has suggested that glutamate-driving neurotransmission and glutamate-excitotoxicity are modulated by substance P in the basal ganglia, but the assembly of glutamate receptors mediating this process remains to be delineated. By using a double immunofluorescence, cellular expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits (GluR1-4) in substance P receptor (SPR)-containing neurons was examined in the striatum of rats. It revealed that distribution of SPR-immunoreactive neurons completely overlapped with that of GluR1, 2, 3 or 4-immunoreactive neurons in the caudate-putamen. Neurons showing both SPR and AMPA receptor subunits (except of GluR3)-immunoreactivity were observed: all (100%) of SPR-positive neurons displayed GluR1-, GluR2- or GluR4-immunoreactivity, and the double-labeled neurons constituted about 33, 3 or 29% of total GluR-positive ones. In contrast, the neurons exhibiting both SPR- and GluR3-immunoreactivity were not detected, though numerous GluR3-positive neurons were still distributed in the caudate-putamen regions. Co-localization of SPR and distinct AMPA receptor subunits in the striatal neurons has provided a basis for functional modulation of neuronal APMA receptors by substance P in the caudate-putamen of rodents. Taken together with previous observations, this study has also suggested that, through interaction with AMPA receptors composed of subunits 1, 2 and 4, substance P or neurokinin peptides may play important roles in regulating neuronal properties and protecting neurons from excitotoxicity in the basal ganglia of mammals.
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PMID:Differential expression of AMPA receptor subunits in substance P receptor-containing neurons of the caudate-putamen of rats. 1519 76

Corticostriatal and thalamostriatal projections utilize glutamate as a neurotransmitter in mammals and birds. The influence on striatum is mediated, in part, by ionotropic AMPA-type glutamate receptors, which are heteromers composed of GluR1-4 subunits. Although the cellular localization of AMPA-type subunits has been well characterized in mammalian basal ganglia, their localization in avian basal ganglia has not. We thus carried out light microscopic single- and double-label and electron microscopic single-label immunohistochemical studies of GluR1-4 distribution and cellular localization in pigeon basal ganglia. Single-label studies showed that the striatal neuropil is rich in GluR1, GluR2, and GluR2/3 immunolabeling, suggesting the localization of GluR1, GluR2 and/or GluR3 to the dendrites and spines of striatal projection neurons. Double-label studies and perikaryal size distribution determined from single-label material indicated that about 25% of enkephalinergic and 25% of substance P-containing striatal projection neuron perikarya contained GluR1, whereas GluR2 was present in about 75% of enkephalinergic neurons and all substance-P -containing neurons. The perikaryal size distribution for GluR2 compared to GluR2/3 suggested that enkephalinergic neurons might more commonly contain GluR3 than do substance P neurons. Parvalbuminergic and calretininergic striatal interneurons were rich in GluR1 and GluR4, a few cholinergic striatal interneurons possessed GluR2, but somatostatinergic striatal interneurons were devoid of all subunits. The projection neurons of globus pallidus all possessed GluR1, GluR2, GluR2/3 and GluR4 immunolabeling. Ultrastructural analysis of striatum revealed that GluR1 was preferentially localized to dendritic spines, whereas GluR2/3 was found in spines, dendrites, and perikarya. GluR2/3-rich spines were generally larger than GluR1 spines and more frequently possessed perforated post-synaptic densities. These results show that the diverse basal ganglia neuron types each display different combinations of AMPA subunit localization that shape their responses to excitatory input. For striatal projection neurons and parvalbuminergic interneurons, the combinations resemble those for the corresponding cell types in mammals, and thus their AMPA responses to glutamate are likely to be similar.
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PMID:Cellular localization of AMPA type glutamate receptor subunits in the basal ganglia of pigeons (Columba livia). 1621 96

Two distinct classes of nociceptive primary afferents, peptidergic and non-peptidergic, respond similarly to acute noxious stimulation; however the peptidergic afferents are more likely to play a role in inflammatory pain, while the non-peptidergic afferents may be more characteristically involved in neuropathic pain. Using multiple immunofluorescence, we determined the proportions of neurons in the rat L4 dorsal root ganglion (DRG) that co-express AMPA or NMDA glutamate receptors and markers for the peptidergic and non-peptidergic classes of primary afferents, substance P and P2X(3), respectively. The fraction of DRG neurons immunostained for the NR1 subunit of the NMDA receptor (40%) was significantly higher than that of DRG neurons immunostained for the GluR2/3 (27%) or the GluR4 (34%) subunits of the AMPA receptor. Of all DRG neurons double-immunostained for glutamate receptor subunits and either marker for peptidergic and non-peptidergic afferents, a significantly larger proportion expressed GluR4 than GluR2/3 or NR1 and in a significantly larger proportion of P2X(3)- than SP-positive DRG neurons. These observations support the idea that nociceptors, involved primarily in the mediation of neuropathic pain, may be presynaptically modulated by GluR4-containing AMPA receptors.
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PMID:AMPA and NMDA glutamate receptors are found in both peptidergic and non-peptidergic primary afferent neurons in the rat. 1867 21