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)

Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization.
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PMID:Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus. 1709 38

Methamphetamine (METH) is an addictive psychostimulant that induces damage to the dopamine terminals and the apoptosis of some neurons of the striatum. Our laboratory demonstrated using either a single bolus dose (30 mg/kg) or a binge (10 mg/kg 4x at 2-h intervals) of METH that pharmacological blockade of the substance P receptor (neurokinin-1) attenuates METH-induced damage to both the presynaptic dopamine terminals and the apoptosis of some neurons of the striatum. To determine the phenotype of striatal neuron ablated by METH, we combined TUNEL (Terminal Deoxyncleotidyl Transferase-Mediated dUTP Nick End Labeling) with immunofluorescence for selective markers of projection and interneurons. METH induces the loss of approximately 20% of the projection neurons. The cholinergic and gamma-aminobutyric acid (GABA)-parvalbumin interneurons sustain losses of 30% and 50%, respectively. The somatostatin/neuropeptide Y (NPY)/nitric oxide synthase (NOS) interneurons are not impacted by METH. To investigate the mechanism by which substance P mediates METH-induced damage in this part of the brain, we ablated the striatal interneurons that express the neurokinin-1 receptor (NK-1R) with the selective neurotoxin substance P-SAP. Ablation of the NK-1R-expressing interneurons prevented METH-induced apoptosis in the striatum but was without effect on depletion of dopamine terminal markers. We propose that substance P mediates the apoptosis of some striatal neurons via the intrastriatal activation of nitric oxide synthesis. In contrast, substance P may mediate damage of the dopamine terminals via an extrastriatal mechanism involving the substantia nigra and cortical glutamate release.
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PMID:Distinct mechanisms mediating methamphetamine-induced neuronal apoptosis and dopamine terminal damage share the neuropeptide substance p in the striatum of mice. 1710 11

In order to investigate epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy (DRPLA), we immunohistochemically examined the expression of neurotransmitters, neuropeptides, calcium-binding proteins and/or glutamate transporters in the brainstem and cerebral cortex in autopsy cases. The subjects comprised 14 cases of clinicopathologically confirmed DRPLA, including 7 cases of juvenile and 2 cases of early adult types with progressive myoclonus epilepsy (PME), 5 cases of late adult type without PME, and 10 age-matched controls. Serial sections of the brainstem and cerebral cortex were treated with antibodies to tyrosine hydroxylase, tryptophan hydroxylase, substance P, methionine-enkephalin, parvalbumin, calbindin-D28K, calretinin, and excitatory amino acid transporters. Although the size of the tegmentum was small, we failed to find any PME-specific brainstem changes in the expression of neurotransmitters, neuropeptides and calcium-binding proteins. The number of interneurons immunoreactive for calbindin-D28K and parvalbumin, markers of GABAergic inhibitory interneurons, were reduced throughout the cerebral cortex, but there was no significant difference in the density of immunoreactive neurons between DRPLA patients of each type. The expression of glutamate transporters was comparatively spared. The current study revealed an absence of PME-specific brainstem lesions and indicated a possible involvement of the reduced GABAergic interneurons in the cerebral cortex in formation of PME in DRPLA.
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PMID:Neuropathological analysis of the brainstem and cerebral cortex lesions on epileptogenesis in hereditary dentatorubral-pallidoluysian atrophy. 1730 19

The anterior thalamic nuclei (ATN) encompass a large region of the anteromedial aspect of the human thalamus. Three ATN have been classically described: anteroventral (AV), anteromedial (AM) and anterodorsal (AD). The present study has carried out histochemical and immunohistochemical procedures in the ATN of normal individuals to analyze whether these nuclei are chemically distinct. The markers used in this study were acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), the calcium binding proteins calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR), and the neuropeptides substance P (SP) and enkephalin (ENK). Other cytoarchitectural and myeloarchitectural techniques, specifically Nissl and Gallyas stainings, were used to delineate the boundaries of the ATN. The main findings of this study are: 1) AChE was very abundant in the AD and was irregular or heterogeneously distributed in the AV and AM; 2) LAMP immunoreactive (ir) neuropil was present throughout the ATN and its distribution was heterogeneous in the AV and AM; 3) the ATN harbored CB-, PV- and CR-ir neurons and neuropil; and, 4) the neuropeptide analysis revealed numerous SP positive varicose fibers scattered throughout the ATN in contrast to very few ENK-ir varicose fibers. These morphological findings describe a heterogeneous chemical anatomy in the human ATN which may reflect regional differences in the functional organization of the ATN with respect to the other thalamic nuclei and the cerebral cortex.
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PMID:Chemical parcellation of the anterior thalamic nuclei in the human brain. 1730 82

It has been reported that application of substance P (SP) to the medial portion of the entorhinal cortex (EC) induces a powerful antiepileptic effect (Maubach et al. [1998] Neuroscience 83:1047-1062). This effect is presumably mediated via inhibitory interneurons expressing the neurokinin-1 receptor (NK(1)R), but the existence of NK(1)R-expressing inhibitory interneurons in the EC has not yet been reported. The present immunohistochemical study was performed in the rat to examine the existence and distribution of NK(1)R-expressing neurons in the EC as well as any co-expression of other neurotransmitters/neuromodulators known to be associated with inhibitory interneurons: gamma-aminobutyric acid (GABA), parvalbumin (PARV), calretinin (CT), calbindin (CB), somatostatin (SST), and neuropeptide Y (NPY). Our results indicated that NK(1)R-positive neurons were distributed rather sparsely (especially in the medial EC), primarily in layers II, V, and VI. The results of our double-immunohistochemical staining indicated that the vast majority of NK(1)R-expressing neurons also expressed GABA, SST, and NPY. In addition, CT was co-expressed in a weakly stained subgroup of NK(1)R-expressing neurons, and CB was co-expressed very rarely in the lateral EC, but not in the medial EC. In contrast, SP-immunopositive axons with fine varicosities were distributed diffusely throughout all layers of the EC, appearing to radiate from the angular bundle. SP may be released in a paracrine manner to activate a group of NK(1)R-expressing entorhinal neurons that co-express GABA, SST, and NPY, exerting a profound inhibitory influence on synchronized network activity in the EC.
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PMID:Immunohistochemical characterization of substance P receptor (NK(1)R)-expressing interneurons in the entorhinal cortex. 1736 10

Bilirubin encephalopathy (BE), which includes acute (kernicterus) and chronic (postkernicteric) forms, results from severe neonatal jaundice. In order to investigate neurodegenerative mechanisms in autopsy cases of BE, we immunohistochemically examined expressions of neurotransmitters, neuropeptides, and calcium-binding proteins in the basal ganglia; and deposition of oxidative products. Expression of tyrosine hydroxylase was reduced in the putamen in cases of acute BE, and in the globus pallidus in cases of acute and chronic postkernicteric BE. Methionine-enkephalin expression was reduced in the external segment of the globus pallidus in cases of acute and chronic postkernicteric BE, and immunoreactivity for substance P was severely altered in both internal and external segments in cases of chronic postkernicteric BE. A decrease in the number of parvalbumin-immunoreactive interneurons in the external segment of the globus pallidus was observed predominantly in cases of acute BE, whereas the number of interneurons immunoreactive for calbindin-D28K was reduced in the putamen in cases of chronic postkernicteric BE. Nuclear immunoreactivity for 8-hydroxy-2'-deoxyguanosine was seen in the putamen in half of the BE cases. These findings indicated that the putamen was impaired in BE and the pallidal external segment was also damaged in the acute form of BE, suggesting that oxidative damage to DNA is implicated in lesions of the basal ganglia.
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PMID:Bilirubin encephalopathy: a study of neuronal subpopulations and neurodegenerative mechanisms in 12 autopsy cases. 1793 77

Gamma-aminobutyric acid(A) (GABA(A)) receptors (GABA(A)R) are inhibitory heteropentameric chloride ion channels comprising a variety of subunits and are localized at postsynaptic sites within the central nervous system. In this study we present the first detailed immunohistochemical investigation on the regional, cellular, and subcellular localisation of alpha(1), alpha(2), alpha(3), beta(2,3), and gamma(2) subunits of the GABA(A)R in the human substantia nigra (SN). The SN comprises two major regions, the SN pars compacta (SNc) consisting of dopaminergic projection neurons, and the SN pars reticulata (SNr) consisting of GABAergic parvalbumin-positive projection neurons. The results of our single- and double-labeling studies demonstrate that in the SNr GABA(A) receptors contain alpha(1), alpha(3), beta(2,3), and gamma(2) subunits and are localized in a weblike network over the cell soma, dendrites, and spines of SNr parvalbumin-positive nonpigmented neurons. By contrast, GABA(A)Rs on the SNc dopaminergic pigmented neurons contain predominantly alpha(3) and gamma(2) subunits; however there is GABA(A)R heterogeneity in the SNc, with a small subpopulation (6.5%) of pigmented SNc neurons additionally containing alpha(1) and beta(2,3) GABA(A)R subunits. Also, in the SNr, parvalbumin-positive terminals are adjacent to GABA(A)R on the soma and proximal dendrites of SNr neurons, whereas linear arrangements of substance P-positive terminals are adjacent to GABA(A) receptors on all regions of the dendritic tree. These results show marked GABA(A)R subunit hetereogeneity in the SN, suggesting that GABA exerts quite different effects on pars compacta and pars reticulata neurons in the human SN via GABA(A) receptors of different subunit configurations.
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PMID:Differential localization of GABAA receptor subunits within the substantia nigra of the human brain: an immunohistochemical study. 1808 88

Sensory trigeminal innervation is a consistent feature of extraocular muscles across species, in spite of a variable occurrence of muscle spindles. We studied the histochemical properties of trigeminal ganglion (TG) cells projecting to the extraocular eye muscles to obtain more information about their function. In monkey TG neurons were retrogradely filled by tracer injections (cholera toxin subunit B; wheat-germ agglutinin) into the belly or myotendinous junction of eye muscles; one conjunctival injection served as a control. Retrogradely labelled TG neurons were processed for the presence of parvalbumin (PV), substance P (SP), or nitric oxide synthase (NOS) by double-immunofluorescence. The results indicate that approximately 10% of trigeminal afferents to all parts of the eye muscle are PV-positive, whereas around 20% are SP-positive. Twice as many SP-positive TG projection neurons were counted after a conjunctival tracer injection, presumably relaying nociceptive signals. A surprisingly large population of NOS-positive TG cells (30%) was found only after distal tracer injections. Up to now none of these TG cell groups could be related to the palisade endings located at the myotendinous junction.
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PMID:Histochemical characterisation of trigeminal neurons that innervate monkey extraocular muscles. 1871 77

Several lines of evidence indicate that peripheral 5-HT2A receptors are involved in the development of inflammatory and neuropathic pain. However, their localization in sensory cell bodies is not accurately known. We therefore studied 5-HT2A receptor distribution in rat lumbar dorsal root ganglia using immunocytochemistry. Forty percent of L3 lumbar dorsal root ganglion cells were immunoreactive for 5-HT2A receptor. Most were small- to medium-sized cell bodies. Double-labeled experiments revealed that they expressed various chemical phenotypes. The smaller 5-HT2AR cell bodies often bind the isolectin B4 although some 5-HT2AR cell bodies also express substance P (SP). Many 5-HT2A-positive small dorsal root ganglion cells expressed the capsaicin receptor transient receptor potential vanilloid type 1 receptor (TRPV1), confirming their nociceptive nature. In addition, a few large cell bodies were labeled for 5-HT2A, and they also expressed NF200 suggesting that they were at the origin of Adelta or Abeta fibers. A total absence of double labeling with parvalbumin showed that they were not proprioceptors. 5-HT2A immunoreactivity in dorsal root ganglia cells was found in the cytoplasm and along the plasma membrane at the interface between sensory cell and the adjacent satellite cells; this distribution was confirmed under the electron microscope, and suggested a functional role for the 5-HT2A receptor at these sites. We therefore investigated the presence of 5-HT and 5-HIAA in lumbar dorsal root ganglia by high performance liquid chromatography. There were 5.75+/-0.80 ng 5-HT and 3.19+/-0.37 ng 5-hydroxyindoleacetic acid (5-HIAA) per mg of protein with a ratio 5-HIAA/5-HT of 0.67+/-0.10, similar to values typically observed in brain tissues. These findings suggest that 5-HT, via the 5-HT2AR, may be involved in the peripheral control of sensory afferents, mainly unmyelinated nociceptors and to a lesser extent neurons with Adelta or Abeta fibers, and in the control of cellular excitability of some dorsal root cell bodies through a paracrine mechanism of action.
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PMID:The 5-HT2A receptor is mainly expressed in nociceptive sensory neurons in rat lumbar dorsal root ganglia. 1936 28

Early comparative embryogenesis can reflect the organization and evolutionary origins of brain areas. Neurogenesis in the auditory areas of sauropsids displays a clear core-to-shell distinction, but it remains unclear in mammals. To address this issue, [3H]-thymidine was injected into pregnant mice on consecutive embryonic (E) days (E10-E19) to date neuronal birthdays. Immunohistochemistry for substance P, calbindin, and parvalbumin was conducted to distinguish the core and shell auditory regions. The results showed that: 1) cell generation began at E13 in the external or dorsal nucleus of the inferior colliculus (IC), but it did not start in the caudomedial portion of the central nucleus of IC, and significantly fewer cells were produced in the medial and rostromedial portions of the central nucleus of IC; 2) cells were generated at E11 in the dorsal and medial divisions of the medial geniculate complex (MGd and MGm, respectively), whereas cell generation was absent in the medial and rostromedial portions of the ventral medial geniculate complex (MGv), and fewer cells were produced in the caudomedial portion of MGv; 3) in the telencephalic auditory cortex, cells were produced at E11 or E12 in layer I and the subplate, which receive projections from the MGd and MGm. However, cell generation occurred at E13-E18 in layers II-VI, including the area receiving projections from the MGv. The core-to-shell distinction of neurogenesis is thus present in the mesencephalic to telencephalic auditory areas in the mouse. This distinction of neurogenesis is discussed from an evolutionary perspective.
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PMID:Evolutionary significance of delayed neurogenesis in the core versus shell auditory areas of Mus musculus. 1948 1

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