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)

Chemotherapy-induced emesis has a major adverse impact on patients undergoing therapy for various malignancies, and this has led to considerable research in this field. Most investigative efforts have concentrated on the acute phase of emesis that occurs within the first 24 hours after chemotherapy, and significant strides forward have been made with this problem. Better control of acute emesis with newer agents such as the serotonin 5-HT3 receptor antagonists has focused increasing attention on a second phase of nausea and vomiting, known as delayed emesis, which occurs more than 24 hours after chemotherapy. This delayed phase is often not as well controlled with the antiemetics that have proven effective in acute emesis, and contributes to the distress associated with emetogenic chemotherapy. Most of the available data on delayed emesis are based on studies with cisplatin-based regimens, with much less understanding of delayed nausea and vomiting induced by non-cisplatin-based chemotherapy. Nevertheless, it is evident that the patterns of delayed emesis associated with cisplatin and non-cisplatin chemotherapy have distinct differences. The control of delayed emesis, especially following cisplatin, remains a therapeutic challenge. Contributing to the lack of progress has been the absence of an experimental model to help in elucidating the pathophysiology of delayed emesis and in the evaluation of new therapeutic approaches. The combination of metoclopramide and dexamethasone, although superior to placebo in randomised trials, provides only moderate control of delayed emesis following high-dose cisplatin. The 5-HT3 receptor antagonists that are effective in the prevention of acute emesis with cisplatin have failed to make a major impact on the delayed phase. When combined with dexamethasone, these agents provide no additional benefit to that achieved using dexamethasone alone or dexamethasone combined with metoclopramide. With non-cisplatin chemotherapy, corticosteroids and 5-HT3 receptor antagonists are the most useful agents. Efforts are ongoing to identify more effective treatments for delayed emesis. One novel approach involves the blockade of substance P binding to neurokinin-1 (NK1) receptors. This article reviews what is currently known about chemotherapy-induced delayed emesis, with a focus on treatment strategies.
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PMID:Drug treatment of chemotherapy-induced delayed emesis. 911 14

We investigated the effect of neuropeptides, which are vasoactive intestinal polypeptide (VIP), substance P, (SP), neuropeptide Y (NPY), neurokinin A (NKA), somatostatin (SOM), calcitonin gene-related peptide (CGRP), and leucine-enkephalin (L-ENK), on the invasion of murine Colon 26-L5 adenocarcinoma cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. VIP, SP, NPY, and L-ENK reduced invasive potential of tumor cells in a concentration-dependent manner, whereas SOM, CGRP, and NKA had no effect. Especially, VIP showed the most effective in inhibiting tumor invasion, and achieved 50% reduction at 10(-6) M. A similar effect by VIP was also observed in cell migration to fibronectin. VIP had no effect on the growth of tumor cells at the concentrations ranging from 10(-10) to 10(-6) M. The suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor. These results indicate that VIP, among the neuropeptides used, could inhibit Matrigel invasion of Colon 26-L5 carcinoma cells through partial suppression of their motility, and the reduction was associated with an intracellular cAMP-mediated pathway.
Cancer Lett 1997 Jun 03
PMID:Differential effect of intestinal neuropeptides on invasion and migration of colon carcinoma cells in vitro. 1837 31

Regulatory peptides are small, readily diffusable and potent natural substances with a wide spectrum of receptor-mediated actions in humans. High affinity receptors for regulatory peptides such as somatostatin, substance P, vasoactive intestinal peptides, and cholecystokinin can be overexpressed in several human diseases, in particular in neoplasms, and represent therefore new molecular targets for cancer diagnosis and therapy. The availability of suitable regulatory peptide radioligands, which can be labeled with radioactive iodine or indium, makes peptide receptor scintigraphy a particularly useful new in vivo diagnostic tool, as seen with the example of somatostatin receptor scintigraphy (Octreoscan). The present article reviews the current in vitro data on regulatory peptide receptor expression in normal and diseased tissues, which represent the basis for the in vivo application of these molecules in nuclear medicine.
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PMID:Regulatory peptide receptors as molecular targets for cancer diagnosis and therapy. 920 45

The neuropeptides substance P, vasoactive intestinal polypeptide, and the recently discovered peptide secretoneurin are neurotransmitters of the intrinsic nervous system of the gut and effect gut motility. The aim of this study was to investigate whether these neuropeptides are involved in the pathophysiology of large bowel ileus. Five patients underwent colonic resections for obstructive cancer of the colon. Full-thickness specimens of the resected colon were taken 10 cm proximal and 10 cm distal to the site of tumor obstruction. Substance P-, vasoactive intestinal polypeptide-, and secretoneurin-like immunoreactivities were measured in the specimens by radioimmunoassay. In addition immunocytochemistry was performed. Tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin were lower in the prestenotic than in the poststenotic bowel segment. In accordance, immunocytochemistry revealed a denser staining of ganglion cells and fibers for all three neuropeptides in the poststenotic bowel. The decreased tissue levels of substance P, vasoactive intestinal polypeptide, and secretoneurin in the prestenotic bowel segment may contribute to the final decompensation of obstructive ileus.
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PMID:Obstructive ileus of large bowel is associated with low tissue levels of neuropeptides in prestenotic bowel segment. 924 56

Immunocytochemical and biochemical studies have indicated the presence of many neuroactive substances in the stomatogastric nervous system (STNS) of the crab Cancer borealis. In electrophysiological studies, many of these substances modulate the motor output of neural networks contained within this system. Previous work in the STNS suggested the presence of neuropeptides related to the invertebrate tachykinin-related peptide (TRP) family. Here we isolate and characterize two novel peptides from the C. borealis nervous system that show strong amino acid sequence identity to the invertebrate TRPs. The central nervous systems of 160 crabs were extracted in an acidified solvent, after which four reversed-phase HPLC column systems were used to obtain pure peptides. A cockroach hindgut muscle contraction bioassay and a radioimmunoassay (RIA) employing an antiserum to locustatachykinin I (Lom TK I) were used to monitor all collected fractions. The amino acid sequences of the isolated peptides were determined by Edman degradation. Mass spectrometry and chemical synthesis confirmed the sequences to be APSGFLGMR-NH2 and SGFLGMR-NH2. APSGFLGMR-NH2 is approximately 20-fold more abundant in the crab central nervous system than is SGFLGMR-NH2. We have named these peptides Cancer borealis tachykinin-related peptide Ia and Ib (CabTRP Ia and Ib), respectively. Both peptides are myoactive in the cockroach hindgut muscle contraction bioassay, with CabTRP Ia being approximately 500 times more potent than CabTRP Ib. RIA performed on HPLC-separated C. borealis stomatogastric ganglion (STG) extract revealed that CabTRP Ia is the only detectable TRP-like moiety in this ganglion. Incubation of synthetic CabTRP Ia with the isolated STG excited the pyloric motor pattern. These effects were suppressed by the broad-spectrum tachykinin receptor antagonist Spantide I. Spantide I had no effect on the actions of the unrelated endogenous peptide proctolin in the STG. There was no consistent influence of CabTRP Ib on the pyloric rhythm. Given its amino acid sequence and minimal biological activity in the crab, CabTRP Ib may be a breakdown product of CabTRP Ia.
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PMID:Two novel tachykinin-related peptides from the nervous system of the crab Cancer borealis. 931 66

[D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P is a broad-spectrum neuropeptide growth factor antagonist that has exhibited in vitro activity against a range of human cancer cell lines. The fate of this compound in vivo following i.p. administration at 12 micrograms/g to nu/nu mice bearing the H69 small-cell lung cancer xenograft has been studied. Metabolism was confined to the C-terminus producing [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P acid and [D-Arg1,D-Phe5,D-Trp7,9]substance P(1-10). The peptide had a long half-life in plasma (45.9 min) and became widely distributed among the tissues studied with the highest accumulation observed in the liver (AUC 1102 micrograms/g x min) and the lowest in the brain (5 micrograms/g x min). Uptake into the tumor xenograft was poor (AUC 189 micrograms/g x min); however, uptake into the lungs was much greater (AUC 507 micrograms/g x min), offering encouragement that therapeutic concentrations may be targeted to primary lung tumors.
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PMID:Processing of [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P in xenograft bearing Nu/Nu mice. 935 69

The neuropeptide substance P (SP), by stimulating tachykinin NK1 receptors (NK1R), triggers a number of biological responses in human glioma cells which are potentially relevant for tumour growth. First, radioligand binding studies demonstrated the presence of tachykinin NK1R on SNB-19, DBTRG-05 MG and U373 MG, but not on U138 MG and MOG-G-GCM human glioma cell lines. Second, application of SP or neurokinin A (NKA) to NK1R+ glioma cell lines increased the secretion of interleukin 6 (IL-6) and potentiated IL-6 secretion induced by IL-1beta. SP also up-regulated the release of transforming growth factor beta1 (TGF-beta1) by the U373 MG glioma cell line. Third, SP induced new DNA synthesis and enhanced the proliferation rate of NK1R+, but not of NK1R- glioma cell lines. Also, NKA stimulated the proliferation and cytokine secretion in NK1R+ glioma cell lines. All the stimulant effects of SP/NKA on NK1R+ glioma cell lines were completely blocked by a specific tachykinin NK1R antagonist, MEN 11467. These data support the potential use of tachykinin NK1R antagonist for controlling the proliferative rate of human gliomas.
Br J Cancer 1999 Jan
PMID:Substance P activates responses correlated with tumour growth in human glioma cell lines bearing tachykinin NK1 receptors. 988 63

We investigated the effect of various neuropeptides present in the prostate, including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of PC-3 prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the invasive capacity of tumor cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon and PTH-rP had no significant effect. Both CGRP and GRP also increased the haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These three neuropeptides had no effect on either adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cells at concentrations used in this study. These results indicate that both GRP and CGRP increased the invasive potential of PC-3 cells probably through enhancement of cell motility, while SP inhibited the invasiveness through suppression of motile response.
Cancer Lett 1998 Nov 13
PMID:Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells. 992 57

[Arg6,D-Trp7,9,NmePhe8]-substance P (6-11) (antagonist G) is a novel class of anti-cancer agent that inhibits small-cell lung cancer (SCLC) cell growth in vitro and in vivo and is entering phase II clinical investigation for the treatment of SCLC. Although antagonist G blocks SCLC cell growth (IC50 = 24.5 +/- 1.5 and 38.5 +/- 1.5 microM for the H69 and H510 cell lines respectively), its exact mechanism of action is unclear. This study shows that antagonist G stimulates apoptosis as assessed by morphology (EC50 = 5.9 +/- 0.1 and 15.2 +/- 2.7 microM for the H69 and H510 cell lines respectively) and stimulates c-jun-N-terminal kinase (JNK) activity in SCLC cells (EC50 = 3.2 +/- 0.1 and 15.2 +/- 2.7 microM). This activity is neuropeptide-independent, but dependent on the generation of reactive oxygen species (ROS) and is inhibited by the free radical scavenger n-acetyl cysteine. Furthermore, antagonist G itself induces inflammation (59% increase in oedema volume compared to control) and potentiates (by 35-40%) bradykinin-induced oedema formation in vivo. In view of these results we show that, as well as acting as a 'broad-spectrum' neuropeptide antagonist, antagonist G stimulates basal G-protein activity in SCLC cell membranes (81 +/- 12% stimulation at 10 microM), thereby displaying a unique ability to stimulate certain signal transduction pathways by activating G-proteins. This novel activity may be instrumental for full anti-cancer activity in SCLC cells and may also account for antagonist G activity in non-neuropeptide-dependent cancers.
Br J Cancer 1999 Jun
PMID:[Arg6,D-Trp7,9,NmePhe8]-substance P (6-11) activates JNK and induces apoptosis in small cell lung cancer cells via an oxidant-dependent mechanism. 1036 11

We have developed a fluorescence-based mix and read method for the quantitative determination of receptor-ligand binding interactions. This method was used to determine IC(50) values for peptide ligands of two endogenous seven-transmembrane receptors that are expressed in cultured human cancer cells. Substance P, neurokinin A, and galanin were labeled with Cy5 and were shown to retain their native binding affinities. The cell-associated fluorescence was quantified using a fluorometric microvolume assay technology (FMAT) scanner that was designed to perform high-throughput screening assays in multiwell plates with no wash steps. The binding of fluorescently labeled substance P and neurokinin A was tested on the human astrocytoma cell line UC11 that expresses endogenous NK(1) receptor. Galanin binding was measured on endogenous galanin type 1 receptors in the Bowes neuroblastoma cell line. IC(50) values were determined for substance P, neurokinin A, and galanin and were found to correspond well with reported values from radioligand binding determinations. To demonstrate FMAT as instrumentation for high-throughput screening, it was utilized to successfully identify individual wells in a 96-well plate in which Cy5-substance P binding in UC11 cells was competed with unlabeled substance P. In addition, we developed a two-color multiplex assay in which cells individually expressing neuropeptide Y and substance P receptors were mixed in the same well. In this assay, the fluorescent ligands substance P and neuropeptide Y bound only to their respective cell types and binding was specifically competed. Therefore, two different seven-transmembrane receptor targets can be tested in one screen to minimize reagent consumption and increase throughput.
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PMID:Determination of ligand binding affinities for endogenous seven-transmembrane receptors using fluorometric microvolume assay technology. 1041 87


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