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 habenulo-interpeduncular system of the rat constitutes an interesting model to address quantitatively problems related to synaptogenesis and to the interactions between neuronal populations after selective alteration of these elements during development. In the present study this has been achieved by experimentally reducing, through gestational treatment with methylazoxymethanol acetate (MAM), the population of cholinergic neurons of the medial habenula which projects to the interpeduncular nucleus. Immunohistochemical analysis gave evidence that the topographical localization of the cholinergic and the substance P-containing populations in the medial habenula was not altered by MAM treatment. Furthermore, the topographical distribution of cholinergic fibers and terminals in the interpeduncular nucleus, which reflects the habenulo-interpeduncular projection as well as cholinergic projections coming from different sources, was substantially preserved. The same was also true concerning the terminal distribution of substance P in the interpeduncular nucleus. Quantitative radioassays demonstrated a sizable decrease of overall ChAT activity in both the habenulae and the interpeduncular nucleus. By comparison of 1 month-old and 3 month-old animals it appeared that this effect was partially reversed with age in the interpeduncular nucleus.
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PMID:Immunohistochemistry and neurochemistry of the habenulo-interpeduncular connection after partial developmental depletion of habenular cholinergic neurons in the rat. 138 20

Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to habenula-target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal habenular cholinergic afferents. This pattern of results implies regulation by the IPN of habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal.
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PMID:Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus. 149 56

The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the "flower pot" test, and assayed (1) normal adult rats, (2) FR-lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus. 149 57

An important component of neuronal development is the matching of neurotransmitter expression with the appropriate target cell. We have examined how peptide transmitter expression is controlled in a simple model system, the avian ciliary ganglion (CG). This parasympathetic ganglion contains 2 distinct types of neurons: choroid neurons, which project to vasculature in the eye's choroid layer and use somatostatin as a co-transmitter with ACh, and ciliary neurons, which innervate the ciliary body and iris and use ACh but no known peptide co-transmitter. We have found that the earliest developmental stage in which neurons with somatostatinlike immunoreactivity (SOM-IR) are consistently found in vivo is stage 30 (embryonic day 6.5), a time shortly after the extension of neurites to targets in the eye's choroid layer. In cell culture, CG neurons expressed SOM-IR in co-culture with choroid cells, but not when cultured with striated muscle myotubes or with ganglion non-neuronal cells. No significant differences in neuronal survival or in ChAT activity were observed under these different co-culture conditions, which suggests that somatostatin expression is independently regulated. The stimulation of somatostatin expression was also specific in that other neuropeptides commonly found in autonomic neurons [neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP)] were not induced in the presence of choroid cells. The ability to stimulate SOM-IR was not contact dependent because a macromolecule of greater than or equal to 10 kDa in choroid-conditioned medium (ChCM) was found to stimulate somatostatin expression in a dosage-dependent fashion. The somatostatin-stimulating activity induced SOM-IR in more than 90% of CG neurons, as well as in retrogradely labeled ciliary neurons, which would not normally express SOM-IR. Thus, the expression of somatostatin in cultured CG neurons is regulated by a macromolecule produced by cells in the choroid layer, a target normally innervated in vivo by CG neurons expressing somatostatin.
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PMID:Stimulation of somatostatin expression in developing ciliary ganglion neurons by cells of the choroid layer. 167 9

Immunocytochemical studies of the vestibular nuclei (VN) were done in the squirrel monkey and cat using polyclonal antisera. Brain stem sections were processed using the Avidin-Biotin peroxidase complex with diaminobenzidine as the chromagen. Choline acetyltransferase immunoreactivity (ChAT-IR) was most prevalent in the caudal medial (MVN), inferior (IVN) and peripheral superior (SVN) VN. Nearly all cells of groups x and z were ChAT-positive. None of the giant cells of the lateral vestibular nucleus (LVN) was ChAT-IR. Glutamate immunoreactivity (GLU-IR) was abundant in all VN and in cells of the vestibular ganglion (VG). Gamma-aminobutyric acid immunoreactivity (GABA-IR), was found in cells of rostral MVN, cell group y and in granules about giant cells in dorsal LVN. Substance P immunoreactive (SP-IR) was present in a small cells in MVN, IVN and the VG and in granules surrounding all large cells in LVN in both monkey and cat; SP-IR granules were most intense in ventral LVN in the monkey. Some cells in the dorsal parts of the fastigial nucleus (FN) were outlined by SP-IR granules in both species. Leucine-enkephalin immunoreactivity (ENK-IR) was identified only in granules surrounding cells of group x in the monkey. GLU was the only immunoreactive substance found in the giant cells of LVN. The disposition of ChAT-IR in the VN suggested participation in commissural systems, as well as projections to spinal cord and/or cerebellum. Small GABA-IR neurons in MVN probably represented both commissural and projection neurons; GABA-IR granules about cells in dorsal LVN and some cells in MVN and SVN appeared to represent Purkinje cell (PC) terminals. SP-IR granules surrounding cells in ventral LVN appeared to represent terminals of small SP-positive VG cells. The source of SP-IR granules around cells in dorsal LVN and some cells in FN and SVN remains unknown, but these fibers may originate from portions of the reticular formation known to contain large numbers of SP-positive neurons.
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PMID:Immunocytochemical features of the vestibular nuclei in the monkey and cat. 170 74

We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.
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PMID:Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. 171 Jun 57

In this study immunohistochemistry is used to investigate the distribution of opioid peptides, substance P (SP), neuropeptide Y (NPY) and acetylcholine (ChAT) in the olfactory tubercle (OT) of the cat. On the basis of our histochemical findings we divide the OT into two parts: the cortical part and the cap regions, the latter containing the granule cell islands. The cortical part shows an intensely ir-punctate staining pattern (opioid and SP), similar to that observed in the striatum, to which it is connected via plexus bridges. The pyramidal neurons representing the main cell type of the cortical part are ir-negative. NPY-ir neurons invade the OT via the plexus bridges from the striatum and are restricted to the cortical part. A different staining pattern exists in the cap regions: dwarf and small pyramidal-like cells display opioid- and SP-like immunoreactivity and therefore are clearly separated from the cortical part. The intensely stained axonal plexus of the cap-region neurons occupies the hilus regions dorsal to the granule islands. In addition, dendrites of large pallidal neurons densely enmeshed in opioid- and SP-ir fibers (woolly fibers) enter the OT from the dorsally located ventral pallidum, pass through the hilus, traverse the granule islands and reach the dwarf cell layer, where the ir-axons apparently terminate. The granule islands do not receive ir-terminals and the granule cells are ir-negative, except some SP-positive granules in the medial islands. Within the hilus regions some large neurons are ChAT-positive, but the majority is ir-negative. The hilus neurons are regarded as the main target of the cap region efferent system. The findings of this study parallel and confirm our morphological observations (Meyer and Wahle 1986).
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PMID:The olfactory tubercle of the cat. II. Immunohistochemical compartmentation. 242 79

The concentration of substance P-like immunoreactive material (SPLI) and somatostatin-like immunoreactive material (SLI) and the activity of acetyl-CoA: choline-O-acetyltransferase (ChAT; EC 2.3.1.6) were measured in eight brain regions of 13 normal patients and 12 patients with Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). SPLI was significantly lower in five of eight regions in the patients with AD/SDAT. Younger patients with AD/SDAT had significantly lower SLI in the parietal cortex than older patients. ChAT activity and SPLI in the parietal cortex of the presenile patients with AD/SDAT were not significantly different from values found in older patients.
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PMID:Cortical substance P-like immunoreactivity in cases of Alzheimer's disease and senile dementia of the Alzheimer type. 617 86

It has become increasingly clear that immune cytokines perform growth and differentiation functions in the nervous system similar to those performed in the immune system. In previous studies we have shown that interleukin-1 beta (IL-1 beta) raises substance P (SP) and the mRNA coding for its preprotachykinin precursor in cultured sympathetic superior cervical ganglia (SCG) (Jonakait and Schotland, 1990; Hart et al., 1991a). The action of IL-1 is blocked both by depolarization of the ganglia and by glucocorticoid hormones (Hart et al., 1991a). In the present report, we have found that IL-1 does not act directly upon neurons to raise SP, but rather induces the production of a soluble intermediate molecule that raises both SP and the cholinergic-specific enzyme ChAT. Its induction by IL-1 is blocked by the synthetic glucocorticoid hormone dexamethasone; its action is compromised under depolarizing conditions. Because medium conditioned by IL-1 (IL-1CM) is functionally similar to leukemia inhibitory factor (LIF), we sought to determine whether this molecule might be an active constituent of IL-1CM. Immunoprecipitation with an antiserum directed against LIF eliminated large proportions of SP-inducing activity from IL-1CM. In addition, steady-state levels of mRNA coding for LIF are increased by IL-1 treatment of SCG. These data suggest that LIF, induced by IL-1, may ultimately be responsible for the IL-1 induction of SP.
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PMID:Interleukin-1 induces substance P in sympathetic ganglia through the induction of leukemia inhibitory factor (LIF). 768 75

The effects of a novel prolyl endopeptidase inhibitor (PEP), (S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)- 1-pyrrolidinecar-boxamide (JTP-4819), on performance of the Morris water maze task and on central cholinergic function were investigated in aged rats. Spatial memory (escape latency, path length, and swimming speed to the platform) was impaired in aged rats performing the Morris water maze task when compared to young rats. Administration of JTP-4819 (1 mg/kg, p.o.) for 14 days improved this memory deficit in aged rats, as shown by the decrease in escape latency and path length. In addition, when JTP-4819 (at doses of 1 and 3 mg/kg, p.o.) was administered for 3 wk, it reversed the age-related increase of ChAT activity in the cerebral cortex and the decrease of 3H-choline uptake in the hippocampus. These data suggest that JTP-4819 ameliorates age-related impairment of spatial memory and partly reverses central cholinergic dysfunction, possibly due to the enhancement of neuropeptide function by inhibition of PEP mediated degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone.
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PMID:Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on spatial memory and central cholinergic neurons in aged rats. 907 79

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