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)

An involvement of neurogenic components in the pathogenesis of psoriatic lesions has been suggested and neuropeptides are thought to play a modulatory role in cutaneous inflammation. In this study, we evaluated the immunoreactivity of the neuropeptides vasoactive intestinal polypeptide (VIP) and substance P (SP) in the skin of patients with chronic plaque psoriasis, by immunohistochemistry and radioimmunoassay. No differences were observed, by immunohistochemistry, in the expression and localization of VIP and SP between psoriatic and normal skin. Using the radioimmunologic technique on whole skin homogenates, VIP levels were significantly increased in psoriatic lesions as compared to normal skin. By contrast, SP levels were significantly lower in lesional and non-lesional psoriatic skin than in normal skin. In addition, we examined the effect of VIP and SP on the proliferation of cultured normal human keratinocytes. VIP (1-28) (1 nM-1 microM) as well as VIP fragments (10-28) (1 nM-1 microM) and (22-28) (1 nM-1 microM) stimulated the proliferation of keratinocytes in a dose-dependent manner, whereas the VIP fragment (1-12) (1 nM-1 microM) was ineffective. The VIP antagonist (N-Ac-Tyr1, D-Phe2)-GRF (1-29)-NH2 (0.1 microM) significantly inhibited the VIP effect on keratinocytes. On the other hand, SP (0.1 microM) not only failed to stimulate keratinocyte growth, but also blocked the VIP-induced stimulation of these cells. The imbalance of cutaneous VIP and SP and their disparate effects on the proliferation of normal human keratinocytes in culture would suggest that these peptides are involved in the pathogenesis of psoriasis and may exert different modulatory activities in the mechanisms underlying the psoriatic lesion.
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PMID:Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes. 137 39

The effects of substance P (SP) in rat spinal cord on the humoral immune response to sheep red blood cells (SRBC) were investigated by the hemolytic plaque-forming cell (PFC) technique. Radioimmunoassay was used for assessing SP content. Catecholamines contents were measured by high performance liquid chromatography (HPLC) with electrochemical-detection. The results suggest that SP in the spinal dorsal horn, but not in the lateral horn, could inhibit the thymus-dependent humoral immune response to SRBC, and this inhibitory effect might be related to the influence of dorsal horn SP on thymic activity. Increased SP content in the spinal dorsal horn at the peak of a humoral immune response might suppress the immune response and play a negative feedback role, preventing excessive immune response.
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PMID:[Effects of substance P in rat spinal cord on the humoral immune response to SRBC]. 137 10

One of the major events involving inflammatory processes is the alteration of microcirculatory hemodynamics by inflammatory mediators released from tissue components. Using modern macrocirculatory techniques, 15 mu radioisotope labeled microspheres, 133Xe washout, laser Doppler flowmetry and double isotopes, 125 and 131I-albumin, and microcirculatory methods, intravital fluorescence microscopy with FITC labeled dextran, we have examined the effects of selected mediators, e.g. 5-hydroxytryptamine (5-HT), prostaglandin E2 (PG-E2), bradykinin (BK), substance P (SP), calcitonin gene related peptide (CGRP) and histamine on blood flow and vascular permeability in the pulp of experimental animals. Surprisingly, SP and CGRP caused weak albumin leakage in the pulp, while the opposite is true in high compliance tissues, such as muscles, suggesting that the vessels in a low compliance environment, such as the pulp, may not be as permeable in response to selected mediators. Intraarterial injection of 5-HT caused a strong vasoconstriction which was mediated by 5-HT1p receptor subtype. The pulpal 5-HT receptor subtype was identified by immunocytochemistry, receptor autoradiography and functional investigations. Intravital fluorescence microscopy observations of the rat incisor preparation showed that histamine, BK and PGE2 increased permeability, whereas isoproteranol caused partial inhibition of the BK-induced increase. In an induced pulpal inflammation model using plaque extract, blood flow increased over 40% in the moderately inflamed pulp, which demonstrated severe vasodilation and polymorpholeukocyte accumulation. In the partially necrotic pulp, blood flow decreased nearly 35%. Results of this study clearly show that there is a high structural/functional correlation in pulpal microcirculation in inflammation. As demonstrated in this presentation, the effects of inflammatory mediators on pulpal microcirculatory hemodynamics are complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of selected inflammatory mediators on blood flow and vascular permeability in the dental pulp. 150 95

In murine schistosomiasis, granulomas form around parasite ova which lodge in the liver and intestines. The granulomas contain eosinophils which produce substance P. In order to demonstrate substance P release by individual granuloma eosinophils and mechanisms regulating this release, a reverse hemolytic plaque assay was developed. Release of substance P was demonstrated by plaque formation around granuloma eosinophils only when a specific substance P antiserum was used. Few cells released substance P in the basal state. However, eosinophils produced plaques in the presence of calcium ionophore A23187 or histamine. Plaque size and number were dependent upon secretagogue concentration. It is thus concluded that granuloma eosinophils can release substance P in response to both pharmacological and physiological agents.
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PMID:Release of substance P by granuloma eosinophils in response to secretagogues in murine schistosomiasis mansoni. 168 39

Neonatal capsaicin treatment has previously been shown to diminish the primary antibody response of adult rats to the subcutaneously administered T-dependent antigen, sheep red blood cells, as measured using a modification of the Cunningham plaque-forming cell assay technique. We have now studied the kinetics of this response in adult normal, neonatally capsaicin-pretreated and neonatally capsaicin-pretreated substance P-infused rats, and examined the effects of the tachykinin antagonist Spantide, on the plaque-forming cell response. Capsaicin pretreatment did not affect the antigen-specific plaque-forming cell response over the first 4 days following antigen injection. At days 5, 6 and 7 of the response, there was a statistically significant decrease in the number of plaque-forming cells secreting antigen-specific IgM, an effect not observed in capsaicin-pretreated rats which were given a subcutaneous infusion of substance P at the time of antigen injection. The tachykinin antagonist Spantide inhibited the plaque-forming cell response in normal rats after in vivo infusion at the time of antigen injection by more than 70%. This effect of Spantide was dose dependent, occurred with maximal effect at 10 microM, and appeared to be independent of any histamine-mediated action. The results of this study provide further evidence for a receptor-mediated immunomodulatory role of tachykinin-containing primary afferent nerves.
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PMID:Effects of capsaicin treatment on immunoglobulin secretion in the rat: further evidence for involvement of tachykinin-containing afferent nerves. 168 77

Evidence for the involvement of primary afferent nerves and their associated neuropeptides in in vivo immunologic responses has been based on experiments in rats in which destruction of primary afferent nerves by the sensory neurotoxin capsaicin results in a diminished ability of the animal to mount a primary antibody response to sheep red blood cell (SRBC) antigen. This effect was shown to be reversed by substance P infusion immediately following antigenic stimulation. In this report we show that neurokinin A (NKA) is 12 times more potent than substance P in its capacity to reverse the effects of neonatal capsaicin pretreatment on the antibody response. Neurokinin A has a pD2 of 6.65 compared to 5.98 for substance P. In addition, NKA was more potent than substance P in reversing the effects of surgical lesions 2 days prior to antigenic stimulation. The effects of the D- and L-Pro9 analogues of [Glp6, Pro9]-SP6-11 on the plaque-forming cell response in capsaicin-treated rats provide further support for the hypothesis that the tachykinin receptor modulating the primary antibody response is an NK-2 receptor. These results demonstrate, for the first time, a role for NKA in in vivo immunomodulation.
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PMID:Tachykinin-mediated modulation of the primary antibody response in rats: evidence for mediation by an NK-2 receptor. 170 44

Neuropeptides including SP and VIP modulate Ig secretion by in vitro stimulated lymphocyte cultures. It is not known whether these neuropeptides effect the B cell directly, or if they significantly alter humoral immune responses to pathogens. We have previously shown that granulomas derived from schistosome-infected mice contain immunoglobulin secreting B cells (ISC) as well as eosinophils that secrete substance P (SP) and vasoactive intestinal peptide (VIP). It therefore seemed plausible that B cells derived from infected animals might respond to these neuropeptides, and that such responses might effect immunoregulatory signals. In this study, we addressed these issues in the murine Schistosoma mansoni model, at the level of immunoglobulin secretion in single B cells. Spontaneous ISC were observed in both splenic and granuloma cell preparations. The addition of SP resulted in a dose-dependent reduction in the number and size of plaques (a 50% reduction was observed at 10(-9) M). This effect was blocked with SP antagonists. Similar results were observed in T cell-depleted cell cultures. VIP had no effect on ISC number or plaque size. We conclude that SP, but not VIP, decreases spontaneous ISC number and Ig secretion in short-term cultures of spleen and granuloma cells. SP appears to exert its effects at the level of single B cells through a receptor-mediated mechanism and may thus play an immunoregulatory role in schistosomiasis.
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PMID:Substance P but not vasoactive intestinal peptide modulates immunoglobulin secretion in murine schistosomiasis. 170 26

The undecapeptide substance P (SP) contained in primary afferent nerves is thought to mediate that part of the neurogenic inflammatory response consisting of vasodilation and plasma extravasation. This response is diminished in rats pretreated as neonates with the neurotoxin capsaicin. It is not known whether primary afferent nerves influence cellular responses of the immune response to antigenic stimulation. Using 6- to 12-wk-old Sprague-Dawley rats pretreated as neonates with capsaicin, we examined the regional lymph node response to a s.c. antigenic stimulus of sheep red blood cells. The number of cells secreting antigen-specific antibody in these animals was reduced by more than 80% using direct and indirect plaque assay methods. The reduced antibody response in capsaicin-pretreated animals was reversed by a s.c. infusion of SP given over a 4-hr period at the injection site immediately after antigen stimulation. This response had a threshold at approximately 1.0 X 10(-5) M SP. SP1-7 (1.0 X 10(-5) M) was without effect but an infusion of SP5-11 (1.0 X 10(-5) M) reversed the effects of capsaicin treatment indicating a carboxyl-terminal effect of SP. The results suggest that the reduced response of capsaicin-treated animals to an antigenic stimulus is due to an effect of capsaicin on the SP-containing primary afferent nerves rather than a toxic effect of capsaicin on the immune system.
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PMID:The effect of substance P on the regional lymph node antibody response to antigenic stimulation in capsaicin-pretreated rats. 244 15

The aim of the present study was to extend our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic, and that substance P mediates the inflammation. For this purpose, the pattern of neurofilament-positive sensory nerve fibers was studied and the lengths and substance P content of these fibers measured morphometrically in dermal and epidermal compartments of the psoriatic lesion, psoriatic but lesion-free skin, and control skin. The epidermis and dermis of the psoriatic lesions were significantly more densely innervated with neurofilament-positive fibers than either lesion-free psoriatic or control skin. Although substance P is known to be rapidly degraded in tissues, and its actual concentrations in the sections were unknown, there was an increase in substance P containing nerves in the psoriatic lesion, the increase being significant in the epidermal nerve fibers. No significant differences in the measured parameters were obtained between lesion-free psoriatic and control skin. These results indicate that there is an altered pattern of sensory nerves in a psoriatic plaque and that substance P may be an important mediator in the inflammatory processes that contribute either to the initiation or maintenance of a psoriatic lesion.
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PMID:Quantification of cutaneous sensory nerves and their substance P content in psoriasis. 279 54

Substance P (SP)-like immunoreactive cells were identified in postmortem white matter tissue from patients with multiple sclerosis (MS). Labelled cells, which by morphologic criteria could be identified as astrocytes, were located at the edge of both active (e.g. inflammatory) and inactive (e.g. non-inflammatory) MS lesions. By contrast, SP-immunoreactive astrocytes were not found in normal controls and were only occasionally present in other conditions associated with astrogliosis. These data suggest that SP, a potent mediator of vasodilatation and local immune responses, may play a role in the genesis of the MS plaque. These results also extend the repertoire of potential interactions which may occur between astrocytes and cells of the immune system.
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PMID:Substance P immunoreactive astrocytes are present in multiple sclerosis plaques. 248 Aug 34


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