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 effects of beta-amyloid protein 1-40 (beta AP 1-40), substance P (SP), and the amidated and carboxylic acid C-terminated forms of the SP homologous beta AP fragment 25-35 (beta AP 25-35-NH2 and beta AP 25-35-COOH) were studied on [3H]MK-801 binding to the rat brain NMDA receptor cation channel. All peptides gave dose-dependent enhancements of [3H]MK-801 binding stimulated by low glycine. beta AP 25-35-COOH, but not beta AP 25-35-NH2 produced an inhibition of [3H]MK-801 binding stimulated by high glycine in the presence of either low or high glutamate. Low glutamate-stimulated [3H]MK-801 binding was also inhibited by SP but not by beta AP 1-40. It is concluded that beta AP related peptides exert differential effects on the NMDA receptor complex at the glycine and possibly also the glutamate recognition sites.
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PMID:beta-Amyloid related peptides exert differential effects on [3H]MK-801 binding to rat cortical membranes. 751 97

The primary constituent of the senile plaque core in Alzheimer's disease (AD) is the beta-amyloid protein (beta A4). A discrete 11 amino acid fragment of the beta A4, beta A4(25-35), has been implicated in mediating in vitro neurotoxicity and an inflammatory response surrounding senile plaques in AD via interaction with the Serpin Enzyme Complex (SEC) receptor. Substance P (SP), a neuropeptide of the tachykinin family and a major mediator of neurogenic inflammation, shows sequence homology to beta A4(25-35) and has been shown to protect against the neurotoxicity of beta-amyloid. SP also competes with beta A4(25-35) for binding to the SEC-receptor. SP neurons have also been found to be depleted in AD. Using a blister model of inflammation in the rat hind footpad, we have examined the effect of beta A4(25-35) and its interaction with SP in rat skin microvasculature and determined age-related changes to these phenomena. In addition, pharmacological manipulation of these responses using SEC-receptor ligands (peptide 105Y and 105C) was also undertaken. Because of the evidence for co-existence and co-release of SP and calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory nerves, it was of interest to examine the interaction of CGRP with beta A4(25-35) on rat skin microvasculature. beta A4(25-35) (10 microM) was perfused over the base of a blister raised on the hind footpad of anaesthetised young and old rats. This was followed by perfusion of SP (1 microM) or CGRP (1 microM) after Ringer's solution. Relative blood flow was monitored using a Laser-Doppler Flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta A4(25-35) modulates substance P effect on rat skin microvasculature in aged rats: pharmacological manipulation using SEC-receptor ligands. 752 33

The present study investigated the effect of substance P (SP) and protein kinase inhibitors (H7 and HA1004) on beta-amyloid peptide-induced proliferation of neonatal rat brain cells in primary cultures. The beta-amyloid peptide1-28 (designated as beta AP28), at nanomolar concentrations (10(-9) M), significantly (P < or = 0.05) increased the proliferation of brain cells (presumably non-neuronal) as measured by [3H]thymidine uptake into DNA (mitogenesis). The effect was dependent on time of culture, concentration of beta AP28, and presence of fetal calf serum. The supplementation of SP into cell cultures at time zero reversed the proliferative response of beta AP28. Moreover, the beta AP28-induced proliferation was inhibited by protein kinase inhibitor H7, but not by HA1004. Since H7 is a selective protein kinase C (PKC) inhibitor and SP action involves PKC, we conclude that beta AP28 induces normal brain cell proliferation through PKC pathway of cell signaling.
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PMID:Effect of substance P and protein kinase inhibitors on beta-amyloid peptide-induced proliferation of cultured brain cells. 752 54

The neuropeptide substance P (SP) is a mediator of neurogenic inflammation. Also, beta-amyloid protein (beta AP) can directly activate the cell types involved in inflammatory processes. The relationship between SP and beta AP on their biological actions has attracted much interest. SP is trophic in neuronal cells and protected them against the death induced by beta AP. In this study, we examined the effects of SP and beta-amyloid peptide on cell viability in neutrophil-like HL-60 cells, by means of the WST-1 tetrazolium and lactate dehydrogenase (LDH) release assays. The results showed that SP promoted the cell survival on neutrophil-like HL-60 cells in serum-free conditions. Also, beta-amyloid peptide showed trophic effects rather than toxic in these cells in WST-1 assay, though it is reportedly toxic in neuronal cells.
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PMID:Trophic effects of substance P and beta-amyloid peptide on dibutyryl cyclic AMP-differentiated human leukemic (HL-60) cells. 754 Jul 10

A beta-amyloid protein fragment AP21-35 (tetradeapeptide with amino acid residues 21-35) was found to be a highly selective agonist of substance P receptors (NK-1) among three tachykinin receptor subtypes. This peptide fragment contracted the smooth muscle preparations of guinea pig ileum in a dose dependent manner (EC50 = 22 microM). This activity was completely reversed by CP-96,345-1, a specific antagonist of NK-1 receptors, whereas atropine for NK-3 had no effect. The peptide was inactive in rat vas deferens which contains predominantly NK-2 receptors. These results indicated that AP21-35 is a highly selective agonist for NK-1 receptors. In the radio-ligand receptor binding assay using [125I]-Bolton-Hunter substance P to membranes from guinea pig ileum, the fragment exhibited a distinct dose-response curve (IC50 = 11 microM). All the present data strongly suggest that beta-amyloid protein function as a peptide ligand of substance P receptors with some pathophysiologic activities.
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PMID:Receptor-mediated specific biological activity of a beta-amyloid protein fragment for NK-1 substance P receptors. 768 98

The biological function of the soluble form of the amyloid beta-protein (ABP) was examined by assaying its interaction with neuronal receptors expressed in Xenopus oocytes. ABP weakly activated tachykinin receptors, but in the presence of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4- propionate-type glutamate receptors ABP-induced responses were greatly enhanced. Glutamate and ABP together also induced accumulation of inositol trisphosphate and increases in intracellular Ca2+. These observations suggest that in the presence of glutamate, ABP can activate tachykinin receptors and phosphatidylinositol turnover. ABP may therefore act as a neuromodulatory peptide.
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PMID:Amyloid beta-protein activates tachykinin receptors and inositol trisphosphate accumulation by synergy with glutamate. 768 20

Immunocytochemical techniques were employed to examine the temporal ordering whereby amyloid beta-protein (A beta P) and neuronal elements collectively come together to form senile plaques in Alzheimer's disease (AD). Specifically, we addressed three questions: (1) whether A beta P deposition precedes or follows neuritic changes; (2) whether paired helical filament (PHF) formation is an early or late event in the genesis of the dystrophic neurites which participate in plaque formation; and (3) whether the density of senile plaques displays any relationship with the prevalence of PHF or Alz-50 containing neurons. To address these questions we studied the amygdala from a group of patients with AD, a group of nondemented age-matched individuals exhibiting a sufficient number of senile plaques to be classified by neuropathological criteria as AD, and a group of age-matched controls without AD pathology. Amyloid-bearing plaques were demonstrated by A beta P immunolabeling and thioflavine-S staining. Neuritic changes in the form of dystrophic neurites were observed with the aid of antibodies against PHF, Alz-50, as well as antibodies against several neuropeptides (i.e., substance P, somatostatin, and neurotensin) and the acetylcholine biosynthetic enzyme, choline acetyltransferase. By using a graded range of pathologic changes both within and across the patient population to provide us with a means of evaluating plaque deposition from its earliest to most advanced stages of development, we observed in patients and/or regions of the amygdala displaying a mild degree of pathologic change A beta P deposition in the absence of any neuritic changes. With increasing density of A beta P, however, we began to observe dystrophic neurites within plaques. In regions of relatively few plaques, the dystrophic neurites were immunolabeled only with antibodies against the various neurotransmitters and they lacked evidence of cytoskeletal pathology (i.e., Alz-50 or PHF). Only as the density of A beta P increased further within a region, were dystrophic neurites observed that exhibited Alz-50 or PHF. In no instance did we observe a relationship between the density of A beta P deposition and the density of Alz-50 or PHF-immunoreactive neurons. Collectively, our data suggest that the deposition of A beta P is an early pathologic event in senile plaque formation. Thereafter, swollen neurites can be seen in the vicinity of A beta P. This early neuritic response, which can first be visualized by immunolabeling for one or another transmitter substance, is followed by alterations in the cytoskeleton as recognized initially by antibodies to Alz-50 and subsequently by the presence of PHF.
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PMID:Evidence that transmitter-containing dystrophic neurites precede paired helical filament and Alz-50 formation within senile plaques in the amygdala of nondemented elderly and patients with Alzheimer's disease. 769 48

Within the amygdala of elderly subjects and patients with Alzheimer's disease (AD), we recently found evidence suggesting amyloid beta-protein (A beta P) deposition occurs before the appearance of dystrophic neurites. Moreover, these data suggested dystrophic neurites initially lack evidence of cytoskeletal pathology although with time and further maturation, the dystrophic neurites display an altered cytoskeleton as evidenced by their immunoreactivity to Alz-50 and paired-helical filaments (PHF). These findings are of particular relevance to our understanding of the sequence of pathologic events in AD and thus it has become important to determine whether these events are unique to the amygdala or are representative of a more general pattern which can be found throughout the brain. Using a battery of antibodies to markers that are characteristic of AD pathology (i.e., A beta P, PHF, and Alz-50), three peptidergic neurotransmitters (neurotensin, somatostatin, and substance P), and one neurotransmitter biosynthetic enzyme (choline acetyltransferase), we examined the entorhinal cortex (EC) of three groups of subjects (AD, normal elderly, and a group of nondemented elderly with numerous senile plaques). The EC was studied, in part, because it is well recognized as a brain region displaying severe and, most importantly, early pathologic changes. Like the amygdala, we found evidence that amyloid beta-protein immunoreactive (A beta P-IR) and thioflavine-S-positive senile plaques occur within the EC prior to the appearance of transmitter-, Alz-50-, or PHF-immunoreactive dystrophic neurites. We also observed transmitter-immunoreactive dystrophic neurites in the absence of Alz-50 or PHF-immunolabeled dystrophic neurites and transmitter- and Alz-50-IR dystrophic neurites in the absence of those containing PHF. Collectively, these findings were similar to those seen within the amygdala and thus reinforced the concept that A beta P deposition is the primary event in plaque pathology, and this deposition is subsequently followed by the appearance of dystrophic neurites which retain their transmitter phenotype yet lack an altered cytoskeleton. With time, these dystrophic neurites develop cytoskeletal alterations and become immunoreactive to Alz-50 and PHF.
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PMID:Evidence that transmitter-containing dystrophic neurites precede those containing paired helical filaments within senile plaques in the entorhinal cortex of nondemented elderly and Alzheimer's disease patients. 769 Jun 77

Swollen, bulbous-shaped (dystrophic) neurites are a common pathologic feature of Alzheimer's disease (AD) and represent one of the most abundant neuritic abnormalities within the brains of patients with this disease. In the present study, we sought to determine whether the dystrophic neurites which are observed in association with senile plaques are unique to AD or whether they are characteristic of a more generalized process of neuritic and/or neuronal degeneration which can be observed in other neurodegenerative diseases. To accomplish this, we examined post-mortem brain material from patients with AD, Parkinson's disease (PD), Parkinson's disease with associated AD, Parkinson's disease with dementia yet without AD pathology, Huntington's disease (HD), Pick's disease and normal age-matched controls (NC). Using a battery of antibodies to amyloid beta-protein (A beta P), paired-helical filaments (PHF), tyrosine hydroxylase, substance P, neurotensin, and somatostatin we found that immunolabeled dystrophic neurites of the type characteristically observed in AD, were seen only in cases and in brain regions where A beta P deposition was present. More specifically, brain areas known to display severe afferent and/or local degenerative changes such as the caudate and putamen in all three PD groups, the caudate in the HD cases, and the temporal cortex in the HD and Pick's cases were conspicuously free of these swollen neurites unless A beta P deposition was also present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alzheimer's disease-like dystrophic neurites characteristically associated with senile plaques are not found within other neurodegenerative diseases unless amyloid beta-protein deposition is present. 809 26

It has been reported that a discrete peptide fragment of beta-amyloid protein, beta A(25-35), and neuropeptide substance P (SP) possessed sequence homology and could bind to the serine protease inhibitor (serpin) enzyme complex (SEC) receptor. Thus, it has been thought that these peptides and SEC receptor ligand might have similar biological activities. In the present study, we found that C-terminal amidated beta A(25-35)-NH2, SP, and the SEC receptor ligand, Phe-Val-Phe-Leu-Met(FVFLM), could induce an increase in the intracellular free Ca2+ concentration ([Ca2+]i) in neutrophil-like human leukemic (HL-60) cells. Pretreatment with pertussis toxin (PTX) potently inhibited the increase in [Ca2+]i stimulated by these peptides, suggesting that these responses might be mediated by PTX-sensitive G-proteins. Furthermore, we examined the effect on these responses of t-butyloxycarbonyl-methionyl-leucyl-phenylalanine (BocMLF), which is a competitive antagonist of chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF) at its receptor. BocMLF scarcely inhibited the [Ca2+]i increase stimulated by beta A(25-35)-NH2. However, the increase in FVFLM-induced [Ca2+]i was potently inhibited by BocMLF. The results suggest that the [Ca2+]i activation of beta A(25-35)-NH2 may have a different mechanism from that of FVFLM in neutrophil-like HL-60 cells, which is not mediated by the SEC-receptor.
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PMID:beta-Amyloid peptide, substance P, and SEC receptor ligand activate cytoplasmic Ca2+ in neutrophil-like HL-60 cells: effect of chemotactic peptide antagonist BocMLF. 853 82


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