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 tone of isolated segments of human coronary arteries with manifestations of atherosclerotic lesions was increased by serotonin (10(-6) M) or prostaglandin F2 alpha (10(-6) M). Insignificant endothelium-dependent relaxation induced by bradikinin, calcium ionofore A-23187 or substance P was observed in several segments with marked (plaque) as well as macroscopically invisible sclerotic lesion. Segments of human coronary arteries without sclerotic damage demonstrated endothelium-dependent relaxation in response to activators of endothelial relaxation factor. Functional disturbance of coronary artery endothelium in endothelial relaxation factor production may be one of the causes of increased smooth muscle tonic contractions, responsible for coronary artery spasm underlying angina pectoris and myocardial infarction.
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PMID:[Endothelial function and spasm of the coronary artery]. 342 12

Activities relating to 3 neurotransmitter and 4 neuropeptide systems have been examined in human temporal lobe (post mortem) for their relationships with age and Alzheimer-type changes (senile plaques and cognitive function). Significant alterations with increasing age (from 61 to 92 years) in a series of non-demented cases included a reduction of the cholinergic enzyme, choline acetyltransferase, and an increase in vasoactive intestinal peptide immunoreactivity. In cases of alzheimer's disease the only neurochemical activity investigated which correlated significantly with cognitive impairment (assessed from a Mental Test Score obtained shortly before death) and with the severity of Alzheimer-type abnormalities (senile plaques density) was choline acetyltransferase. Further analyses of the data in relation to the severity of plaque formation suggest that alterations in other neurochemical activities including reductions in dopamine-beta-hydroxylase activity, cholecystokinin octapeptide (aqueous extracted) and somatostatin immunoreactivities and an increase in substance P immunoreactivity, may occur at later stages of the disease process. These comparative data suggest that biochemical changes in this brain area associated with age and earlier stages of Alzheimer's disease may be relatively selective.
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PMID:Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes. 617 77

The immunosuppressive activity of three pentapeptides related to the C-terminal fragments of tachykinins was investigated using the PFC (plaque forming cell) test. The peptides were of the general structure Phe-X-Gly-Leu-Met-NH2, with Tyr, Val and Ile in X position, respectively. The results were compared with those obtained previously for the substance P (SP) C-terminal pentapeptide. It was found that peptides containing aromatic residues in X position were more potent immunosuppressors than peptides containing aliphatic residues in the same position. The results also suggest that in mammalian organisms substance SP may be involved in immunomodulation which is rather not the case with other mammalian tachykinins (neurokinin A and neurokinin B).
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PMID:Immunosuppressive activity of C-terminal fragments of tachykinins. 748 53

The neuroimmunomodulation (NIM) function of substance P (SP) in some brain areas of rats was investigated by the hemolytic plaque-forming cell (PFC) technique for detecting humoral immune function, and by radioimmunoassay for assessing SP content in some brain areas. The results showed that the contents of SP in the hypothalamus, hippocampus and pons were significantly decreased, while SP contents in the hypophysis, midbrain and medulla were not significantly changed at the peak of the immune response to sheep red blood cells (SRBC). Intracerebroventricular injection of capsaicin and SP antiserum had no effect on the immune response to SRBC. These results suggest that the immune response could affect the metabolism of SP in some brain areas, and provide further evidence that the nervous system (NS) can both regulate immune function and be affected by it.
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PMID:[The immune response evokes changes of substance P content in some brain areas]. 752 1

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

We investigated the action of oral naftidrofuryl, a serotonin (5-HT2)antagonist, on atheromatous plaque formation, endothelial function, and neutrophil activity in cholesterol-fed (1% for 12 weeks) rabbits. Cholesterol feeding caused almost complete (84 +/- 4%) coverage of the aortic surface with atheromas and a marked intimal thickening. The endothelium-dependent relaxation to acetylcholine (ACh 1 nM-10 microM) and substance P (30 nM) was considerably reduced, whereas the relaxing effect to the endothelium-independent nitric oxide donor linsidomine (SIN-1) (100 microM) was unchanged. Treatment of hypercholesterolemic rabbits with naftidrofuryl (50 mg/kg body weight) resulted in a marked (54 +/- 6%, p < 0.05) reduction in aortic plaque formation. Endothelium-dependent relaxation to ACh was significantly improved in rings of both thoracic aorta: 33 +/- 5 versus 14 +/- 5% (p < 0.05) and abdominal aorta 68 +/- 9 versus 37 +/- 10% (p < 0.05). Similar results were obtained with substance P, but the responses to SIN-1 were unchanged. Zymosan-induced, luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMN) was markedly stimulated in cholesterol-fed rabbits. Naftidrofuryl reduced this hyperreactivity to that of control rabbits. There was no change by naftidrofuryl in any of these parameters in control rabbits, precluding a direct action of the compound in nonhypercholesterolemic conditions. These data demonstrate significant endothelium-protective actions of long-term oral naftidrofuryl in cholesterol-fed rabbits that involve inhibition of cholesterol-induced neutrophil activation.
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PMID:Antiatherosclerotic effects of oral naftidrofuryl in cholesterol-fed rabbits involve inhibition of neutrophil function. 754 72

ODU Plaque-susceptible rats (ODUS/Odu) exhibit markedly heavy plaque formation in the lower incisors and develop both periodontal pockets and gingivitis after being fed a commercially available powder diet. These rats have been established as an inbred strain. We have demonstrated that the ODUS/Odu are a very suitable experimental model for studying periodontitis. We already reported about the allelic distribution, changes of plaque formation and body weight, biochemical nature, toxic activity, vascular permeability factor and bradykinin inactivating factor of the plaque, histological and immunological studies, the pH in the periodontal pocket, amount of saliva, IgA in the saliva, salivary kallikrein, the relationship between sialic acid in the saliva and the serum, leukocyte functions (chemotaxis and superoxide anion) in ODUS/Odu, histamine, mast cell, free radicals, superoxide dismutase activities in gingiva and gingival nerve fibers with substance P or calcitonin gene-related peptide, and effect of diabetes. Streptozotocin-induced diabetic ODUS/Odu may be a useful tool for studying the pathological mechanisms in the development of periodontal tissue breakdown in diabetes. ODUS/Odu should help to further establish the utility of this strain as a model for experimental periodontal disease.
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PMID:[Experimental periodontitis in rats]. 762 82

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

As part of an ongoing investigation devoted to understanding the pathogenesis of senile plaques, we employed histochemical and immunocytochemical techniques to examine the distribution and cytologic features of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), somatostatin (SOM), neurotensin (NT) and substance P (SP) containing fibers and neurons within the amygdala of: (1) patients with Alzheimer's disease (AD); (2) age-matched non-demented controls (NC); and (3) a group of non-demented cases, who upon postmortem neuropathologic examination exhibited sufficient numbers of senile plaques to be classified as AD. This latter group was referred to as high plaque non-demented (HPND). For every case, the distribution of immunolabeled fibers and neurons were determined for each transmitter throughout the various subnuclei of the amygdala. In addition, in the AD and HPND cases the topographic distribution of senile plaques was determined throughout the amygdala using thioflavine-S and Bielschowsky silver methods. In the amygdala, the distribution and density of senile plaques were not bound by conventional cytoarchitectural groupings but rather were most dense in the ventromedial regions of the amygdala with decreasing density in dorsal and lateral directions. Importantly, the density and distribution of senile plaques failed to correlate with the normal topography and/or density of the various peptidergic or cholinergic fibers within the amygdala. The finding that plaques do not correlate with the topographic distribution of any specific transmitter system suggests that plaques likely do not arise from the degeneration of a single neurotransmitter system (i.e., the cholinergic system). However, the finding that in AD a transmitter is most markedly depleted in regions of greatest plaque density, suggests certain constituents of the plaque (e.g. beta-amyloid) may be contributing to the degeneration of local fibers. The extent to which a transmitter was depleted in AD patients varied considerably among those four investigated with the cholinergic and NT systems displaying the most dramatic reductions, followed by SP and SOM. Despite these differential reductions in fiber density, all four neurotransmitters were found localized within dystrophic neurites and in most instances these dystrophic neurites were associated with thioflavine-positive senile plaques. In contrast to the AD cases, the HPND cases were characterized by no significant reductions in immunolabeled fibers, although immunostained dystrophic neurites were very prevalent in the HPND cases. These data suggest that dystrophic neurites occur very early in the disease process and likely precede the actual loss of fibers when or if it occurs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunocytochemical distribution of peptidergic and cholinergic fibers in the human amygdala: their depletion in Alzheimer's disease and morphologic alteration in non-demented elderly with numerous senile plaques. 824 91


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