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)

Our studies have clearly shown that neuropeptides have a profound effect on immunoglobulin synthesis both in vivo and in vitro. The effects varied according to the neuropeptide added or the tissue from which the lymphocytes were obtained. Substance P caused the most pronounced enhancement of both functions, especially in Peyer's patch cells, where it selectively increased IgA synthesis. Somatostatin was inhibitory, and the effect of vasoactive intestinal peptide varied according to the source of the cells. We have previously shown that neuropeptides also cause mast cell secretion and that only substance P was effective in this regard on intestinal mucosal mast cells. Therefore, we looked for microanatomic relationships between peptidergic nerves and immune effector cells. Mast cells appear to have structural associations with neuropeptides-containing nerves in the intestine. Nerve growth factor, known to promote the growth of sensory afferent and sympathetic nerves, has significant direct effects on mast cells. In vitro, this substance caused enhanced antigen mediated histamine release and, in vivo, extensive mast cell hyperplasia. Also, in humans, we were able to produce increased numbers of mast cell/basophil colonies from peripheral blood in the presence of nerve growth factor.
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PMID:Neuropeptides and immunity. 244 42

The neuropeptides vasoactive intestinal peptide (VIP), substance P, and somatostatin are found in high concentrations in both the central nervous system and the gastrointestinal tract. Specific high affinity receptors for VIP, substance P and somatostatin have been identified on both human and murine lymphocytes, suggesting a role for each of these neuropeptides in a neuroimmune axis. These peptides may be important modulators of mucosal immunity regulating lymphocyte proliferation and trafficking in gut associated lymphoid tissue, synthesis of IgA, and histamine release. Somatostatin antagonism of both VIP and substance P effects has been observed in the immune system. Though the mechanisms by which these neuropeptides modulate immune function have not been completely delineated, current evidence supports the hypothesis that VIP modulates immune function via cAMP dependent pathways while substance P regulation of the immune response involves phospholipid metabolism. Somatostatin inhibition of both cAMP dependent and phospholipid dependent effects has been documented in endocrine tissues. Delineation of the role of these peptide-peptide interactions in modulation of the immune response promises to be a fruitful area for further investigation.
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PMID:Neuropeptide modulation of the immune response in gut associated lymphoid tissue. 245 49

Many experiments have demonstrated that the nervous and immune systems interact in a bidirectional fashion. Neuropeptides, including substance P, have been shown to modulate lymphocyte DNA, RNA and immunoglobulin synthesis in vitro and to play a role in inflammatory and hypersensitivity disease states. However, the role of substance P as an immunomodulator in vivo is uncertain and there is only indirect evidence of this effect obtained in vitro. Therefore, we have assessed the effect of substance in vivo on DNA and immunoglobulin synthesis by murine splenic and Peyer's patch lymphocytes after the continuous administration via a miniosmotic pump of substance P in vivo. Substance P administered in this fashion increased cell proliferation of lymphocytes isolated from both organs. Immunoglobulin synthesis was also increased and in a relatively isotype-specific manner. IgA synthesis was most affected, IgM synthesis less so and IgG synthesis was not changed significantly. These effects of substance P on lymphocytes in vivo are similar to its effects on cell proliferation and immunoglobulin synthesis when cells are exposed to this peptide in vitro. These results provide direct evidence that neuropeptides (substance P) may modulate lymphocyte function in vivo and that neuropeptides should be incorporated into the conceptual framework of immune regulation.
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PMID:In vivo immunomodulation by the neuropeptide substance P. 245 90

We describe here a series of experiments which have been undertaken in the course of several years to try and study secretory mechanisms operative in the release of antibodies in the lumen of the intestine. The results of our experiments suggest that there are a number of stimuli that are efficacious in eliciting antibody release in the lumen of the rat intestine. These include the peptide hormones cholecystokinin and substance P, and cholinergic agonists such as pilocarpine. The fact that food has a similar effect indicates that the stimulation of antibody release is a physiological process co-ordinated with the ingestion of foreign antigens. We have also shown that food mediates its effect by means of cholecystokinin. Cholecystokinin promotes the release of antibodies belonging to the IgA, IgG, IgM and IgE isotypes. There is reason to believe that not all the IgA is secretory IgA. Antibody release can be inhibited by the CCK antagonist proglumide and by cholinergic antagonists. The intracellular messengers that participate in this process are changes in cytosolic calcium. It is proposed that the release of antibodies in the gastrointestinal tract is an active secretory process.
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PMID:A study of stimuli operative in the release of antibodies in the rat intestine. 247 91

In view of the extensive innervation of the gastrointestinal tract, including the mucosa, and the high number of immune effector cells present in this tissue, we have studied the effects of certain neurotransmitters on immune responses. We have concentrated on the effects of the neuropeptides substance P (SP), somatostatin (SOM) and vasoactive intestinal peptide (VIP). We have found that SP causes an increase in the proliferation of Peyer's patch lymphocytes as well as immunoglobulin (especially IgA) synthesis, when compared to splenic cells; and that there is a greater expression of SP receptors on lymphocytes derived from Peyer's patches compared to the spleen, without a significant difference in the expression between subsets of T and B cells. Furthermore, we have shown that intraepithelial leukocytes (IEL) show significantly increased cytotoxic activity following incubation with SP; whereas splenic lymphocytes were not stimulated in the same system. The effects of SOM where bi-directional depending upon the concentration employed but in general, SOM was inhibitory, in terms of proliferation, as was VIP. Although many more experiments are required to prove a physiological significance for the results that we have obtained, and to examine the whole gamut of neurotransmitters, we suggest that neuroendocrine regulation may play an important part in mucosal immunity.
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PMID:Neuroendocrine regulation of mucosal immunity. 265 23

A number of anatomical studies have demonstrated the presence of peptidergic nerve fibers infiltrating mucosal lymphoid tissues. The exact mechanisms of how neuropeptides are released to affect these lymphoid sites are unclear, but radiolabeled binding studies have shown that mucosal leukocytes bear a number of neuropeptide receptors on their cell surfaces capable of responding to neural signals. The presence of neuropeptide-containing fibers and the ability to receive neural signals suggest that mucosal lymphocytes can be influenced by neurogenic mediators. The objectives set forth in this review are to provide what is currently known about the ability of substance P and vasoactive intestinal peptide to promote mucosal IgA responses in the gastrointestinal tract via Th2 mechanisms and to discuss how these neuropeptides contribute to the exacerbation of the inflammatory diseases of the gastrointestinal tract. We describe how immune responses develop in the gastrointestinal immune system and emphasize how neuropeptides may influence the differentiation of lymphocytes in mucosal inductive tissues and their subsequent expression in mucosal effector sites. Finally, we discuss new techniques developed by the Mucosal Immunization Research Group that have enabled the study of mucosal immune responses.
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PMID:The enteric nervous and immune systems: interactions for mucosal immunity and inflammation. 753 Nov 2

The specificity of IgA against food, inhalant, bacterial and fungine antigens as well as for HIV-1 proteins was investigated in 14 HIV-1-infected children (CDC stage P-2) and 15 controls. IgA against food- and inhalant antigens as well as against tetanus toxoid were significantly more often present in the HIV positive children than in controls. No difference between the two groups was present for IgA against Candida albicans. A significant increase of substance P, a strong IgA synthesis inducing neuropeptide, was demonstrated in the plasma of HIV-1 infected children. In conclusion, high levels of IgA seem to reflect a complex immune dysfunction in which many factors are involved. The importance of neuroimmune dysregulation is discussed.
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PMID:High levels of IgA in HIV-1-perinatally-infected children. Antigen specificity and possible role of increased substance P plasma levels. 753 87

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

The effect of vasoactive intestinal peptide (VIP), somatostatin (SOM), and substance P (SP) on spontaneous human IgE and IgG4 production in atopic patients was studied. In cultures of mononuclear cells (MNC), VIP inhibited both IgE and IgG4 production without affecting IgM, IgA, IgG1, IgG2, or IgG3 production. In contrast, SOM inhibited only IgE production whereas SP inhibited only IgG4 production without affecting production of other isotypes or other IgG subclasses. The effect of neuropeptides was specific because each was specifically blocked by a corresponding neuropeptide antagonist. To achieve the effect noted above, neuropeptides must be added at the start of the culture. IFN-alpha and IFN-gamma were found to inhibit both IgE and IgG4 production whereas prostaglandin E2 (PGE2) inhibited only IgE production. However, the inhibition of IgE and IgG4 production by neuropeptides could not have been mediated by IFN-alpha, IFN-gamma, or PGE2 because the addition of anti-IFN-alpha, anti-IFN-gamma, and indomethacin, respectively, did not reverse the inhibition. In contrast to their effects on MNC, neuropeptides did not affect production of either IgE or IgG4 by purified B cells; the addition of either T cells or monocytes to B cells had no effect on this. However, neuropeptides were effective in inhibiting IgE and IgG4 production by B cells cultured together with both T cells and monocytes. Depletion of sIgE+ and sIgG4+ B cells resulted in abrogation of IgE and IgG4 production, respectively. However, stimulation of sIgE- B cells with IL-4 plus anti-CD 40 mAb induced IgE production, which was inhibited by VIP and SOM, but not SP, in the presence of both T cells and monocytes. These results suggest that neuropeptides inhibited spontaneous IgE and IgG4 production by interaction with sIgE+ and sIgG4+ B cells in a T cell- and monocyte-dependent fashion. In addition, VIP and SOM also inhibited IgE production by modulating switching induced by IL-4 plus anti-CD 40 mAb in a T cell- and monocyte-dependent fashion.
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PMID:Effect of vasoactive intestinal peptide, somatostatin, and substance P on spontaneous IgE and IgG4 production in atopic patients. 768 25

From current information, a brief review was made on the basic properties of a possible process of eosinophil activation and degranulation. The "activated" eosinophils show the following characteristics: diminished cell density, morphologic alterations, increased surface receptors, heightened parasite killing, increased metabolic activity and prolonged survival. Immune complexes (secretory IgA, IgG, IgE) are known as potent triggering stimuli of eosinophil degranulation as well as complement fragments (C3b, C3bi). Cytokines (IL-5, GM-CSF), PAF and peptides (substance P) act both as weak degranulation inducer and degranulation enhancer. Synergism between the two pathways, Ca2+ and protein kinase C, is now recognized as a common feature of control of secretion in eosinophils.
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PMID:[Eosinophil granule proteins (MBP, ECP, EPX/EDN, EPO)--a possible process of eosinophil activation and degranulation]. 849 33


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