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 pronounced synovial hyperplasia often found in the joints of patients with rheumatoid arthritis could be explained partially by the action of monocyte-macrophage polypeptides (monokines). This report demonstrates that two cytokines which may be derived from monocyte-macrophage populations, namely platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), stimulate the DNA synthesis and proliferation of human synovial fibroblast-like cells cultured in low (i.e., 1%) fetal bovine serum. Epidermal growth factor, insulin-like growth factor-I, insulin-like growth factor-II (multiplication stimulating activity) and substance P were inactive. Unlike IL-1, PDGF and FGF do not also stimulate PGE2, plasminogen activator, and hyaluronic acid levels. Thus PDGF and FGF, arising from stimulated monocyte-macrophages, may play a role in the stimulation of mesenchymal cell proliferation that often accompanies chronic inflammatory arthritic disease. The synovial cells respond to a variety of cytokines in different ways suggesting multiple-signaling pathways.
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PMID:Stimulation of human synovial fibroblast DNA synthesis by platelet-derived growth factor and fibroblast growth factor. Differences to the activation by IL-1. 270 21

Thymic epithelial cells, including nurse cells (TECs/TNCs), from various species synthesize neuroendocrine-related precursors belonging to neurohypophysial, tachykinin and insulin hormone families. The thymic repertoire of neuroendocrine-related polypeptides illustrates at the molecular level the paradoxical role of the thymus in both T cell positive and negative selection. On the one hand, these precursors are a source of signals which interact with neuroendocrine-type receptors expressed by target pre-T cells according to the cryptocrine type of cell-to-cell signaling. On the other hand, the same precursors constitute a source of self-antigens which are presented to pre-T cells by the thymic major histocompatibility complex system. Basically, the model of thymic T cell education to neuroendocrine self was established by the identification in TECs/TNCs of immunoreactive (ir) oxytocin as the self-antigen of the neurohypophysial family. Nevertheless, through the expression in TECs/TNCs of ir-neurokinin A and ir-insulin-like growth factor-II, the model also applies to the tachykinin and insulin hormone families.
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PMID:Development and evolutionary aspects of thymic T cell education to neuroendocrine self. 867 53

We find that substance P (SP) and insulin-like growth factor-1 (IGF-1) demonstrate a synergistic effect on the stimulation of rabbit corneal epithelial migration in an organ culture. The addition of either SP or IGF-1 alone did not affect epithelial migration, while the combination of SP and IGF-1 stimulated epithelial migration in a dose-dependent fashion. The synergistic effects of SP and IGF-1 on corneal epithelial migration were nulled by the addition of a SP antagonist or enkephalinase. Among neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acethylcholine chloride, norepinephrine, serotonin) or tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin), only SP demonstrated a synergistic effect with IGF-1 on cellular migration. In contrast, the combination of SP and IGF-1 did not affect the incorporation of 3H-thymidine into corneal epithelial cells. The attachment of the corneal epithelial cells to fibronectin, collagen type IV, and laminin matrices increased after treatment of the cells with SP and IGF-1, but SP or IGF-1 by themselves did not affect the attachment of the cells to these extracellular matrix proteins. An identical synergistic effect on corneal epithelial migration was observed when an NK-1 receptor agonist was used in place of SP, suggesting the synergistic effect of SP and IGF-1 might be mediated through the NK-1 receptor system. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors.
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PMID:Synergistic effects of substance P with insulin-like growth factor-1 on epithelial migration of the cornea. 884 32

1. We have previously shown that substance P (SP) and insulin-like growth factor-1 (IGF-1) act synergistically to enhance the migration of rabbit corneal epithelial cells in an organ culture model. The present study was designed to identify the epithelial cell SP receptor that participates in this synergistic effect. 2. Rabbit corneal blocks were incubated for 24 h, then the length of the path of epithelial migration was measured. Reagents tried in the TC-199 culture medium, in the presence or absence of IGF-1, were: SP, agonists of tachykinin receptors NK1, NK2 or NK3 and antagonists of tachykinin receptors NK1 or NK2. 3. The binding characteristics of SP receptors were examined in rabbit cultured corneal epithelial cells by binding assays with [125I]-SP in the presence or absence of excess unlabelled SP or ligands of NK1, NK2 or NK3 receptors. 4. As was demonstrated previously, SP and IGF-1 stimulated epithelial migration when they were added to the culture medium together, but individually they had no effect. NK1 agonists had the same synergistic effect with IGF-1 as did SP, but the NK2 and NK3 agonists did not. Furthermore, the NK1 antagonist abolished the synergistic effect of SP and IGF-1, but the NK2 antagonist had no effect. 5. SP bound specifically to rabbit cultured corneal epithelial cells. The binding affinity was 0.44 nM and there were 2.43 x 10(4) binding sites per cell. The NK1 ligand competed, in a dose-dependent fashion, with the binding of SP to corneal epithelial cells, but neither the NK2 nor NK3 ligand affected binding. 6. We conclude that the SP receptor in rabbit corneal epithelial cells is NK1 and that this receptor participates in the synergistic enhancement of corneal epithelial migration by SP and IGF-1. The precise mechanism(s) of this interaction requires more study. These findings imply that both neural and humoral factors are essential for the maintenance and healing of corneal epithelium.
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PMID:The NK1 receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin-like growth factor-1. 905 Dec 88

Neurotrophic keratopathy, which often follows damage to the trigeminal nerve, is clinically characterized by various types of epithelial disorders and melting of corneal stroma. To understand both the pathology of neurotrophic keratopathy and the physiological significance of corneal sensation, we investigated both the cellular and molecular functions of a sensory neurotransmitter, substance P, in corneal epithelial cells. Our findings prompted us to try a new mode of treatment for neurotrophic keratopathy. Substance P, a member of the tachykinin family, is an 11-amino-acid peptide. In an organ culture system using rabbit corneas, substance P alone had no effect on corneal epithelial migration. In the presence of insulin-like growth factor-1 (IGF-1), however, substance P synergistically facilitated corneal epithelial migration in proportion to the concentration of substance P or of IGF-1. Other neurotransmitters (acetylcholine, norepinephrine, serotonin etc.) or tachykinins (neurokinin A, eledoisin etc.) did not show this synergistic effect with IGF-1. Among receptors for the tachykinin family (NK-1, NK-2, or NK-3) only the NK-1 receptor system was involved in the synergistic effect of substance P and IGF-1 on corneal epithelial migration. IGF-1 affected neither the binding constant nor the number of sites of substance P receptors in corneal epithelial cells, suggesting that the synergistic effect was not regulated at the receptor level. Various extracellular signals activate the intracellular signal transduction system, thus amplifying specific biological functions. We found that the addition of inhibitors of protein kinase C or tyrosine kinase clearly inhibited the synergistic effect of substance P and IGF-1 on corneal epithelial migration, demonstrating that protein kinase C and tyrosine kinase are involved in the synergistic effect. During corneal epithelial wound healing, epithelial cells must attach to a provisional, extracellular fibronectin matrix. We previously reported that interleukin 6 and epidermal growth factor (EGF) facilitate corneal epithelial wound healing by activating the expression of fibronectin receptor (integrin). Reverse transcription-polymerase chain reaction (RT-PCR) revealed that substance P and IGF-1 increased expression of mRNA for integrins alpha 5 and beta 1 in cultured corneal epithelial cells and also increased the number of cells that attached to a fibronectin matrix. These findings strongly suggest that substance P and IGF-1 synergistically increase corneal epithelial migration by activating the expression of integrin. Tachykinins share a five amino acid sequence, phenylalanine-free amino acid-glycine-leucine-methionine amide (FXGLM), at the C-terminus. Studying substance P, we found that a four amino acid sequence at the C-terminus, FGLM, was the minimum amino acid sequence for the synergistic effect on corneal epithelial migration. Structurally similar tetrapeptides mimicking other members of the tachykinin family isoleucine-glycine-leucine-methionine amide (IGLM), valine-glycine-leucine-methionine amide (VGLM), tyrosine-glycine-leucine-methionine amide (YGLM), and the tripeptide glycine-leucine-methionine amide (GLM) did not have any synergistic effect with IGF-1. Based on these findings in vitro, we investigated the effect of eye drops containing substance P plus IGF-1 or FGLM plus IGF-1 on the epithelial wound closure of rabbit corneas in vivo. Both combinations significantly facilitated corneal epithelial wound closure. In a clinical setting, the administration of substance P plus IGF-1 effectively treated corneal epithelial defects in a patient with Riley-Day syndrome, a disease in which corneal epithelial defects persist because of loss of corneal sensation and hypolacrimation. In a patient with neurotrophic keratopathy due to trigeminal nerve paralysis following surgery, eye drops containing FGLM plus IGF-1 eliminated superficial punctate staining. (ABSTRACT TRUNCATED)
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PMID:[Neurotrophic keratopathy--studies on substance P and the clinical significance of corneal sensation]. 943 58

We previously reported that substance P (SP) and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial migration in vitro and in vivo. We wanted to determine whether proteins responsible for cellular attachment are activated in corneal epithelial cells. To do this, we examined changes in tyrosine phosphorylation in focal adhesion kinase (FAK) and paxillin in cultured SV-40 transformed human corneal epithelial cells (HCE cells). HCE cells were cultured in the absence or presence of either SP (2 x 10(-5) M) or IGF-1 (10 ng/ml) or both SP and IGF-1. Treatment of HCE cells by either SP or IGF-1 alone did not alter tyrosine phosphorylation in either FAK or paxillin. However, the combination of SP and IGF-1 significantly increased tyrosine phosphorylation in both FAK and paxillin. In contrast, the combination of SP and IGF-1 was not observed to produce synergistic effects on the activation of mitogen-activated protein kinase in HCE. These results show that the synergistic effects of SP and IGF-1 on corneal epithelial wound healing were expressed through activation of the integrin, FAK, and paxillin system.
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PMID:Up-regulation of phosphorylation of focal adhesion kinase and paxillin by combination of substance P and IGF-1 in SV-40 transformed human corneal epithelial cells. 943 2

To clarify the mechanisms by which substance P (SP) and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial wound healing, we tested the hypothesis that the combination promotes cell attachment to a fibronectin matrix through up-regulation of expression of integrin alpha 5 beta 1, the major cell surface fibronectin receptor in rabbit corneal epithelial cells. Cultured rabbit corneal epithelial cells were treated with SP and/or IGF-1 and then plated on wells coated with fibronectin and bovine serum albumin. After incubation, the number of cells attached to the wells was counted. In a second experiment, reverse transcription-polymerase chain reaction was used to determine the expression of integrin alpha 5 and beta 1 by cells pretreated with SP and/or IGF-1. The combination of SP and IGF-1 significantly increased the number of cells attached to the fibronectin matrix and the expression of integrin alpha 5. However, attachment to the fibronectin matrix was inhibited by the addition of GRGDSP, a synthetic peptide that mimics fibronectin. Thus, the synergistic enhancing effect of SP and IGF-1 on the attachment of corneal epithelial cells to the fibronectin matrix and on corneal epithelial migration is partly due to the up-regulation of integrin alpha 5 expression in corneal epithelial cells.
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PMID:Up-regulation of integrin alpha 5 expression by combination of substance P and insulin-like growth factor-1 in rabbit corneal epithelial cells. 961 88

We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial migration in vivo and in vitro. We investigated whether the substance P-derived tetrapeptide (phenylalanine-glycine-leucine-methionine-amide, FGLM) can up-regulate the receptors for fibronectin and cellular adhesion to fibronectin matrix in the presence or absence of IGF-1 in cultured SV-40 transformed human corneal epithelial (HCE) cells. The combination of both FGLM and IGF-1 and substance P and IGF-1 significantly increased the number of cells adhered to the fibronectin matrix and the expression of integrin alpha5. The synergistic effect of FGLM and IGF-1 on the adhesion of HCE cells to the fibronectin matrix is partly carried through up-regulation of integrin alpha5 expression in HCE cells. These results showed that the four-amino-acid sequence at the C-terminus of substance P completely mimics the substance P molecule in terms of synergism with IGF-1 on adhesion of epithelial cells to the fibronectin matrix.
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PMID:Up-regulation of integrin alpha5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine- amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells. 1004 72

1. We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically stimulate corneal epithelial wound healing in vitro and in vivo. We wished to identify which portion of the amino acid sequence of substance P might be responsible for this synergism. 2. Corneal epithelial migration was not affected by the addition of any one of the following factors: substance P; Phe-Gly-Leu-Met-NH2 (C-terminal of substance P); Val-Gly-Leu-Met-NH2 (C-terminal of neurokinin A, neurokinin B, and kassinin); Tyr-Gly-Leu-Met-NH2 (C-terminal of physalaemin); Ile-Gly-Leu-Met-NH2 (C-terminal of eledoisin); or Gly-Leu-Met-NH2 (common C-terminal of tachykinins). 3. In the presence of IGF-1, only substance P and Phe-Gly-Leu-Met-NH2 were synergistic in stimulating corneal epithelial migration in a dose-dependent fashion. 4. The combination of Phe-Gly-Leu-Met-NH2 and IGF-1 did not affect the incorporation of [3H]-thymidine into corneal epithelial cells. 5. Treatment with Phe-Gly-Leu-Met-NH2 and IGF-1, but not with Phe-Gly-Leu-Met-NH2 or IGF-1 alone, increased attachment of corneal epithelial cells to a fibronectin matrix. 6. The levels of alpha5 and beta1 integrin were not affected by Phe-Gly-Leu-Met-NH2 or IGF-1 alone, but they were significantly increased by the combination of Phe-Gly-Leu-Met-NH2 and IGF-1. 7. Topical application of the same combination facilitated corneal epithelial wound closure in vivo. 8. These results demonstrated that Phe-Gly-Leu-Met-NH2, a sequence of 4 amino-acids of the C-terminal of substance P, is the minimum sequence necessary to produce the synergistic effects of substance P and IGF-1 on corneal epithelial wound healing.
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PMID:Synergistic effect with Phe-Gly-Leu-Met-NH2 of the C-terminal of substance P and insulin-like growth factor-1 on epithelial wound healing of rabbit cornea. 1038 50

Substance P (SP) and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial wound healing in vitro and in vivo. This synergism is mediated through the NK-1 receptors for SP, and IGF-1 does not modulate the binding affinity of NK-1 receptors. To clarify the effect of SP on the binding characteristics of IGF-1 receptors, the binding affinity and number of binding sites for IGF-1 in rabbit corneal epithelial cells were studied using a binding assay for(125)I-IGF-1. The binding affinity and number of binding sites for IGF-1 were determined by Scatchard plot analysis. Cultured rabbit corneal epithelial cells bound specifically to IGF-1. For IGF-1 in corneal epithelial cells, the binding affinity was 4 n m and the number of binding sites was 1x10(5)binding sites cell(-1). Although IGF-2 and insulin also bind to IGF-1 receptors, their affinities were, respectively, eight- and 300-fold lower than that of IGF-1. IGF-1 and IGF-2 stimulated corneal epithelial migration in the presence of SP, but insulin did not. Pretreatment of the corneal epithelial cells with SP (2x10(-5)m) failed to change the binding affinity or number of binding sites for IGF-1. These results demonstrated that corneal epithelial cells possess specific receptors for IGF-1. The synergistic effect of SP and IGF-1 on corneal epithelial wound healing does not result from regulation at the receptor level.
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PMID:Characterization of insulin-like growth factor-1 receptors in rabbit corneal epithelial cells. 1065 45


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