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

Biochemical assays on microdissected samples, denervation studies, subcellular fractionation, and light and electron microscopic autoradiography of high affinity uptake have been performed to study the cellular localization of transmitter candidates in the rat hippocampal formation. High affinity uptake of glutamate and aspartate is localized in the terminals of several excitatory systems, such as the entorhino-dentate fibres (perforant path), mossy fibres (from granular cells) and pyramidal cell axons. Thus, in stratum radiatum and oriens of CA1, 85% of glutamate and asparate uptake and 40% of glutamate and aspartate content are lost after lesions of ipsilateral plus commissural fibres from CA3/CA4. Hippocampal efferents also take up aspartate and glutamate, since these activities are heavily reduced in the lateral septum and mamillary bodies after transection of fimbria and the dorsal fornix. The synthesis (by glutamic acid decarboxylase), content and high affinity uptake of gamma-aminobutyrate (GABA) are not reduced after lesions of these or other projection fibre systems. A localization in intrinsic neurons is confirmed by a selective loss of glutamic acid decarboxylase after local injections of kainic acid. Peak concentrations of the enzyme occur near the pyramidal and granular cell bodies, corresponding to the site of the inhibitory basket cell terminals, and in the outer parts of the molecular layers. Some 85% of glutamic acid decarboxylase is situated in 'nerve ending particles'. Acetylcholine synthesis (by choline acetyltransferase) disappears after lesions of septo-hippocampal fibres. Since 80% of the hippocampal choline acetyltransferase is in 'nerve ending particles', the characteristic topographical distribution of this enzyme should reflect the distribution of cholinergic septo-hippocampal afferents. Serotonin, noradrenaline, dopamine and histamine are located/synthesized in afferent fibre systems. Some monoamine-containing afferents to the hippocampal formation pass via the septal area, others via the amygdala. The hippocampal formation also contains nerve elements reacting with antibodies against neuroactive peptides, such as enkephalin, substance P, somatostatin and gastrin/cholecystokinin.
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PMID:Localization of putative transmitters in the hippocampal formation: with a note on the connections to septum and hypothalamus. 3 19

Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures.
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PMID:Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat. 127 53

The hippocampus contains the highest number of glucocorticoid-sensitive neurons in the rat brain and excessive exposure to glucocorticoids can cause damage to hippocampal neurons and impair the capacity of the hippocampus to survive neuronal insults. In this study in situ hybridization combined with quantitative image analysis was used to study preprotachykinin-A mRNA levels after administration of a toxic dose of kainic acid in animals pretreated with glucocorticoids. Kainic acid was injected into dorsal hippocampus CA3 region in animals pretreated with the synthetic glucocorticoid receptor agonist dexamethasone and in control animals. Preprotachykinin-A mRNA was not detected in the hippocampus of untreated animals or in animals analysed 30 min after a kainic acid injection. However, 4 h after injection of kainic acid, the level of preprotachykinin-A mRNA increased to 20-times above the detection limit both in the dentate gyrus and the CA3 region of the hippocampus. Treatment of kainic acid-injected animals with dexamethasone 30 min before and 2 h after the injection attenuated the increase in the granule cells of the dentate gyrus by 50%. In contrast, dexamethasone pretreatment had no significant effect on the kainic acid-induced increase of preprotachykinin-A mRNA in pyramidal cells in regions CA3 or CA1. These results show that an excitatory stimulus within the hippocampus causes a substantial increase in the level of preprotachykinin-A mRNA in hippocampal granule and pyramidal cells and suggest that in granule cells of the dentate gyrus this increase can be modulated by glucocorticoids.
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PMID:Kainic acid-mediated increase of preprotachykinin-A messenger RNA expression in the rat hippocampus and a region-selective attenuation by dexamethasone. 143 5

Autopsy study of a patient who died after an episode of prolonged unilateral status epilepticus revealed neuronal loss in the hippocampus on the epileptic side, with gliosis confined to the CA1 and CA3 fields. There was loss of the parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)-ergic interneurons in the hippocampus on that side. There was also loss of the normal laminar pattern of substance P staining with increased substance P immunoreactivity in the supragranular plexus on that side. Met-enkephalin immunoreactivity was also increased in the outer molecular layer of the dentate gyrus on the epileptic side. Mossy fibers on the epileptic side stained more strongly with the Hicks' silver stain and with antibodies against glutamate and taurine, but less intensely with antibodies against calbindin. In the contralateral cerebellum, there was Purkinje cell loss, injury to the remaining Purkinje cells, and increased prominence of the Bergmann glia. Our observations show that prolonged unilateral seizure activity can be associated with specific histochemical changes in the human hippocampus.
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PMID:Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. 171 86

Substance P (SP) and substance K (SK) are structurally related peptides which are both encoded in the preprotachykinin A gene. The distribution of SP- and SK-like fibers and cell bodies in the rat hippocampus were studied by immunohistochemistry. The distribution of SK-like fibers was similar to that of SP-like fibers but there were few SK-like fibers. Fibers for both peptides were prominent in the dorsal and ventral subiculum and at the junction of CA2 and CA3. SP- and SK-like cell bodies were noted in the subiculum and in the stratum oriens of CA1 and CA2. SP- and SK-like cells were also noted in the ventral dentate gyrus but only SP-like cells were found in the dorsal dentate gyrus.
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PMID:Comparison of substance K-like and substance P-like fibers and cells in the rat hippocampus. 244 9

An analysis of the distribution of substance P immunoreactive nerve cell bodies and fibres is given for infant and adult human hippocampus by using the peroxidase-antiperoxidase technique of Sternberger. The description covers the substance P distribution in the area dentata, the Ammon's horn, the subicular complex and the entorhinal cortex. Each region shows a specific pattern in its substance P immunoreactivity. In general, the hippocampal neurons occur in three major classes of interneurons: large (20-35 microns) horizontal bipolar or multipolar neurons in the alveus, in the deep part of the subicular complex, the entorhinal cortex, and in the white matter of the angular bundle; small (10-20 microns) and large (20-35 microns) vertically oriented bipolar or multipolar neurons in the stratum oriens, in the stratum pyramidale of the Ammon's horn, and in the deep part of the subicular complex and the entorhinal cortex; large (20-35 microns) multipolar neurons in the hilus. Substance P immunoreactive fibres are particularly abundant around pyramidal cells of the CA2 and CA3 subfields of the Ammon's horn and around granule cells of the area dentata. They are also detected in the fimbria and angular bundle. Comparative study of the infant and adult hippocampus reveals no variation in the area dentata and Ammon's horn except that substance P immunoreactive fibres are more abundant in the molecular layer of the area dentata in adults. In contrast, a far more extensive number of substance P immunoreactive cell bodies are detected in the deep layers of the subicular complex and the entorhinal cortex, as well as in the white matter of the angular bundle in infants aged between three and 12 months old. This rich substance P immunoreactive network raises questions concerning its function within the human hippocampus.
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PMID:Substance P neurons in the human hippocampus: an immunohistochemical analysis in the infant and adult. 326 41

The distribution of substance P-containing fibers within the hippocampal formation of the cat was examined using an immunohistochemical approach. A new, indirect immunoperoxidase method based on the high affinity binding of vitamin H (biotin) by avidin was developed to demonstrate substance P-like immunoreactive fibers. The neocortex contained only occasional single substance P fibers. In contrast, the archicortical structures contained a well organized substance P innervation. The entorhinal area of the parahippocampal gyrus contained a delicate network of varicose axons which appeared to ascend from the subcortical white matter to terminate predominantly in layer II. The subiculum contained a network of positive varicosities throughout the neuropil of both the pyramidal and the molecular layers. These substance P terminals appeared to arise, at least in part, from fibers entering laterally across the angular bundle. Within the ventral hippocampus the substance P innervation was predominantly in the pyramidal cell layer, and was heaviest in field CA3 and weakest in CA1. Some fibers were also observed in strata oriens, lucidum, and radiatum. Occasional varicose fibers could be seen entering the hippocampus from the fimbria. Within the dentate gyrus the substance P fibers were most concentrated in the supragranular layer and among the more superficial of the granule cells. A moderately dense plexus of fibers also occurred in the neuropil of the hilus among the polymorphic cells. In addition, a distinct, narrow band of varicosities was found at the outer edge of the inner molecular layer, while the outer molecular layer did not contain any positive elements. It is concluded that the hippocampal formation receives a distinct, well organized substance P innervation. Substance P fibers appear to enter the hippocampus both laterally across the angular bundle and ventrally through the fimbria. From this detailed examination of the distribution of the substance P fibers within the hippocampus in relation to the other known inputs to this area it is suggested that many of the substance P fibers arise in or, more probably, pass through the septal area to innervate the hippocampus.
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PMID:Organization of substance P fibers within the hippocampal formation demonstrated with a biotin-avidin immunoperoxidase technique. 616 95

This study in the African green monkey (Cercopithecus aethiops) was designed to characterize the neurochemical features of hippocampal nonpyramidal neurons that are specific synaptic targets of substance P-containing projective neurons located in the supramammillary nucleus. Our previous studies provided evidence for an excitatory nature to this hypothalamo-hippocampal pathway and described the mode of termination of these afferents on hippocampal principal neurons. The present correlated light and electron microscopic immunocytochemical analysis, using the nickel-diaminobenzidine/diaminobenzidine double-labeling technique, revealed that this hippocampal afferent system establishes multiple, exclusively asymmetric synapses with three specific subpopulations of nonpyramidal cells: (1) a small portion of parvalbumin-containing basket cells located periodically in or adjacent to the granule cell layer of the dentate gyrus, which therefore inhibit only a subpopulation of granule cells; (2) some of the calbindin-immunoreactive local circuit neurons located in the hilar area; and (3) calbindin-positive cells occurring exclusively in the stratum molecular of the middle portion of the CA3 subfield. Postembedding studies revealed that the aforementioned calbindin-containing cells are GABAergic inhibitory neurons. Our studies indicate that hypothalamic afferents can effectively filter the information flow at different levels of the excitatory signal loop in the monkey hippocampal formation. Dentate granule cells, which are only stimulated by hypothalamic afferents, will transfer excitatory signals differently than those that are controlled by a feedforward inhibitory mechanism initiated by these fibers. In the CA3 subfield, the signal flow can again be depressed by those pyramidal neurons that are inhibited by calbindin-containing cells receiving an excitatory hypothalamic input.
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PMID:Morphological evidence that hypothalamic substance P-containing afferents are capable of filtering the signal flow in the monkey hippocampal formation. 751 94

Possible interactions between sigma (sigma) receptor sites and calcitonin gene-related peptides (CGRP) were investigated using receptor subtype-related analogues and fragment in in vivo [3H](+)SKF 10 047/sigma binding in the hippocampus, and electrophysiological recording of the N-methyl-D-aspartate (NMDA)-induced activation of CA3 pyramidal neurons, two well-established sigma assays. In both paradigms, CGRP and the agonist [Cys(ACM)2,7]hCGRPalpha modulated sigma systems. In vivo binding experiments demonstrated that CGRP and [Cys(ACM)2,7]hCGRPalpha inhibited 25-40% of specific [3H](+)SKF 10 047 labelling in the mouse hippocampal formation while the purported antagonist hCGRP8-37 was inactive. The specificity of this modulation was demonstrated further by the lack of effect of other vasoactive peptides, including the atrial natriuretic peptide, substance P, and its N-terminal fragment, substance P1-7. In the CA3 subfield of the rat dorsal hippocampus, hCGRP alpha decreased (up to 61%) the NMDA-induced activation of the pyramidal neurons. Conversely, the linear analogue [Cys(ACM)2,7]hCGRP alpha enhanced (by 85%) the NMDA-induced activation of CA3 pyramidal neurons, while the antagonistic fragment hCGRP8-37 had no effect. Haloperidol, a high-affinity sigma receptor ligand, inhibited by 90% the in vivo [3H](+)SKF 10 047 labelling, and prevented the modulation of the NMDA-induced activation by hCGRP alpha and [Cys(ACM)2,7]hCGRP alpha. It thus appears that CGRP can modulate sigma-related systems in the hippocampal formation.
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PMID:In vivo modulation of sigma receptor sites by calcitonin gene-related peptide in the mouse and rat hippocampal formation: radioligand binding and electrophysiological studies. 852 71

Light and electron microscopic substance P (SP) immunostaining was performed on hippocampal sections of colchicine-pretreated, control, untreated fimbria-fornix-transected (5 days), as well as perforant path-stimulated Sprague-Dawley rats fixed in 5% acrolein. Numerous SP-immunoreactive neurons could be observed in the stratum oriens of the Ammon's horn and subiculum, fewer were seen in the dentate hilar area and stratum radiatum of CA2 and CA3, and even fewer were seen at the border between the CA1 strata radiatum and the lacunosum moleculare of CA1 subfield. A higher dose of colchicine resulted in SP immunoreactivity in a large population of granule cells and mossy axon terminals. The entire CA2 region, the stratum oriens of CA1, CA3, and the subiculum were densely innervated by SP-containing axon terminals. A homogeneous SP innervation was found in the stratum radiatum of CA1. Only a few SP fibers were seen adjacent to the granule cell layer. Symmetric axosomatic contacts were seen between SP-containing boutons and somata in the stratum oriens of the Ammon's horn. However, throughout the hippocampal formation, the majority of SP-containing axons formed axodendritic symmetric synapses. A dense population of SP-immunoreactive boutons that formed axodendritic asymmetric synapses was observed in the strata oriens and radiatum of the CA3a and CA2 regions, and a few were found in the supragranular and subgranular layers of the dentate gyrus. Fimbria-fornix transection resulted in a marked loss of SP fibers in the strata oriens, pyramidale, and radiatum of the CA3a and CA2 subfields. In perforant pathway-stimulated animals, a population of granule cells and a large number of mossy axon terminals were immunoreactive for SP. These observations suggest two sources of SP innervation to the hippocampal formation: one arising from intrinsic sources (interneurons and granule cells) and one arising from extrinsic sources, most likely the supramammillary region.
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PMID:Substance P innervation of the rat hippocampal formation. 921 39


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