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)

Experimental data strongly suggest that the nervous and immune systems are interrelated. One example of this interrelation is anatomical and is represented by innervation of the lymphoid organs by substance P (SP) immunoreactive fibers, among others. Neurotransmitters/neuropeptides can exert functional receptor-mediated immunologic responses. SP binding to its receptor induces cytokine production in macrophages and T cells and stimulates IgG secretion from B cells. SP has also been associated with inflammation and other immune-mediated diseases such as arthritis. We have previously reported an in vitro stimulatory effect of SP on hematopoiesis that was mediated mostly by the induction of two relevant hematopoietic growth factors, IL-3 and granulocyte-macrophage-CSF (GM-CSF). In this study, we have shown that SP, through the carboxyl terminus, induces the production of IL-3 and GM-CSF in bone marrow mononuclear cells. This production requires de novo synthesis and is blocked by two different SP-R antagonists, spantide and CP-96,345-1. The induction of IL-3 and GM-CSF is partially mediated by IL-1 and IL-6, which are also produced by bone marrow mononuclear cells. Furthermore, the production of IL-3 and GM-CSF correlated with an accumulation of their respective steady state mRNAs. T cells found within the bone marrow are responsible for most of the induced IL-3. Because SP mediates the release of IL-1, IL-3, IL-6, and GM-CSF, all important hematopoietic regulators, by bone marrow cells, this study further suggests the possibility of a regulatory role of the nervous system in hematopoiesis mediated by neuropeptides such as SP.
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PMID:Induction of IL-3 and granulocyte-macrophage colony-stimulating factor by substance P in bone marrow cells is partially mediated through the release of IL-1 and IL-6. 751 64

The tachykinins are a family of neuropeptides that share a common carboxyl terminus. Substance P (SP) and neurokinin-A (NK-A) are derived from the preprotachykinin l gene. Although SP and NK-A can bind to either NK-1, NK-2, or NK-3 receptors (R), they have preferences for NK-1R and NK-2R, respectively. We have reported that SP stimulates erythroid (E) (burst-forming unit [BFU]-E and colony-forming unit [CFU]-E) and myeloid (CFU-granulocyte-macrophage [GM]) progenitors partly through the induction of growth factors. We have now investigated the hematopoietic effects of NK-A using short-term bone marrow (BM) cultures and found that NK-A (10(-7) to 10(-12) mol/L) inhibits CFU-GM proliferation but stimulates erythroid progenitors. Release of soluble factors by the stroma appears to mediate the inhibition because direct contact with the stroma was not required. We have found that NK-A, through NK-2-like receptors induces increased levels of macrophage inflammatory protein-1 alpha (MIP-1 alpha) and transforming growth factor-beta (TGF-beta) (transcriptional and posttranscriptional) in BM stroma. Clonogenic assays with NK-A (10(-9) mol/L) and either anti-MIP-1 alpha or anti-TGF- beta 1 indicate that these cytokines partly contribute to the inhibition, suggesting that these two negative hematopoietic regulators exert part of the inhibition by NK-A on CFU-GM. The findings of two closely related neuropeptides, derived from the same gene, exerting opposite effects on myeloid colonies suggest that neuropeptides, by themselves could be important factors in hematopoietic regulation.
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PMID:Induction of negative hematopoietic regulators by neurokinin-A in bone marrow stroma. 870 7

Following brain injury, astrocytes express receptors for cytokines and neuropeptides and secrete several regulatory mediators that have a well established role in inflammation, immunity, and tissue development or repair. To elucidate the role of substance P (SP), a neurotransmitter peptide of the tachykinin family, in inducing astrocyte secretory activities, we have examined the expression of SP receptors and the functional consequences of their activation in cultured astrocytes from the human embryonic brain or spinal cord. Radioligand binding studies revealed that only one type of SP receptors, the high affinity NK-1 receptor, was present on human astrocytes and that spinal cord astrocytes expressed about 6 times as many SP binding sites as brain astrocytes. Following SP treatment, a substantial inositol phosphate formation was observed in spinal cord astrocytes only. Stimulation of spinal cord astrocytes with SP alone did not induce secretion of cytokines [interleukin-6 (IL-6), granulocyte-macrophage-CSF, macrophage chemoattractant protein-1 or leukemia inhibitory factor] or prostaglandin E2 (PGE2). Interestingly, however, SP selectively potentiated the inducing effect of IL-1beta on IL-6 and PGE2 secretion by spinal cord astrocytes without affecting the IL-1-beta-evoked secretion of other cytokines. SP also enhanced the small inducing effect of tumor necrosis factor-alpha (TNF-alpha) on IL-6 and PGE2 secretion and that of transforming growth factor-beta on PGE2 secretion. These results suggest that SP can enhance immunoregulatory and neurotrophic astroglial functions mediated by IL-6 and PGE2 by acting in concert with a set of cytokines whose cerebral expression has been reported during development and in a variety of diseases.
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PMID:Functional characterization of substance P receptors on cultured human spinal cord astrocytes: synergism of substance P with cytokines in inducing interleukin-6 and prostaglandin E2 production. 933 33

Hematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects. Cytokines, associated with hematopoietic stimulation, and SP regulate the expression of each other in BM mesenchymal and immune cells. Neutral endopeptidase (NEP) uses SP as a substrate to produce SP(1-4), which inhibits the proliferation of matured myeloid progenitor. This study determines whether the degradation of SP to SP(1-4) by endogenous NEP in BM stroma could be a feedback on hematopoietic stimulation by stem cell factor (SCF). SP(1-4) induced the production of transforming growth factor (TGF)-beta and tumor necrosis factor-alpha in BM stroma. TGF-beta production accounted for part of the inhibitory effects by SP(1-4) on the proliferation of early (granulocyte-macrophage colony-forming units) and late (long-term culture-initiating cells) hematopoietic progenitors. Enzyme-linked immunosorbent assays and/or protein-chip arrays indicated a timeline change of SP to SP(1-4) in BM stroma stimulated with SCF, which correlated with increase in NEP messenger RNA. Since SP and its fragment, SP(1-4), interact with the same receptor to mediate opposing hematopoietic effects, 2 interactive studies were done to understand the dual responses of NK-1: (1) a 3-dimensional molecular model of NK-1 and SP and (2) screening of a random dodecapeptide library for SP(1-4) interacting sites. The effects of SP(1-4) on hematopoietic progenitors and the timeline change of SP to SP(1-4), together with the 3-dimensional model, provide a partial explanation for the feedback on the stimulatory effects of SCF and SP on hematopoiesis.
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PMID:Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study. 1167 40