Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronan (HA) in combination with diclofenac is currently undergoing clinical trials as a topical preparation in the management of osteoarthritic pain, basal-cell carcinoma and actinic keratosis. These are clearly diverse pathologies, but in all cases substance P plays a central role either directly or through secondary mediators such as prostaglandin E2 and nitric oxide. A common mechanism for HA in combination with diclofenac in these conditions may be through ameliorating the direct and indirect effects of substance P. Additionally, HA appears to depot and hold diclofenac in the epidermis, thereby prolonging its pharmacokinetic half-life. In rabbits, stenosis following balloon angioplasty is prevented by a subcutaneous dose of HA, probably through blockade of cell-surface HA receptors (ICAM-1, CD44 & RHAMM). The physicochemical properties of HA, and the binding of HA to HA receptors, suggests that HA will have value as a novel drug delivery system.
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PMID:Hyaluronan as a drug delivery system for diclofenac: a hypothesis for mode of action. 886 45

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.
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PMID:Differential effect of intestinal neuropeptides on invasion and migration of colon carcinoma cells in vitro. 1837 31

Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.
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PMID:Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells. 924 51

Although radiotherapy is often used to treat laryngeal carcinoma, there is little information on the effects of this treatment on laryngeal structures. Rats were irradiated to the head and neck region and the larynges were studied by light- and electron-microscopy and immunohistochemistry. Ten days after irradiation, a change in the ultrastructural appearance of the granules of the subglottic glands was observed. Substance P-, bombesin- and enkephalin-like immunoreactivity was increased in local ganglionic cells and glandular nerve fibres. The mast cells were reduced in number. At examination 4 6 months after irradiation, there were no obvious differences compared with controls concerning mast-cell numbers and neuropeptide expression. The ultrastructural changes seen in the subglottic glands remained to some extent. The results show that structural changes in the subglottic glands occur concomitantly with an increased expression of certain neuropeptides in the innervation of these glands, which implies a relationship between these two parameters. The mast cells respond drastically to irradiation, but in the long run, regeneration of these cells occurs.
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PMID:Short- and long-term effects of irradiation on laryngeal mucosa of the rat. 1066 67

The immunohistochemical expression of various neuropeptides, including substance P (SP), and the substance P receptor (SPR), was examined in irradiation-induced enteropathy in man. Samples from irradiated and non-irradiated patients operated on for rectal carcinoma were examined. The samples were from the sigmoid and corresponded macroscopically to non-cancerous sigmoid colon. There was a marked atrophy, ulcerations and inflammatory reactions in the irradiation-influenced mucosa. In this mucosa, there was a very pronounced innervation of varicose nerve fibers showing SP-like immunoreactivity (LI). The degree of SP-LI in the ganglionic cells of the submucous plexus was increased as compared to non-irradiated patients. There were only few or no nerve fibers showing immunoreaction for other neuropeptides examined (CGRP, enkephalin, NPY) in the irradiation-influenced mucosa. A marked SPR immunoreaction was detected in cells in the lamina propria which were interpreted as representing polymorphonuclear leukocytes. The marked expression of SP in the irradiation-damaged mucosa and the presence of SPR immunoreactive leukocytes suggest that SP is highly involved in the inflammatory reactions that occur in response to radiotherapy. The observations also suggest that SP, but not NPY, CGRP and enkephalin, has an important role in the reorganisation processes that take place in the mucosa in irradiation-induced enteropathy.
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PMID:Pronounced substance P innervation in irradiation-induced enteropathy--a study on human colon. 1070 46

Interstitial cystitis (IC) represents a rare and complex inflammatory bladder condition in which diagnostics can be challenging. Strict NIH criteria for its diagnosis were designed for research purposes. Their routine application would miss large proportions of IC patients. When IC is suspected, history and physical exam are followed by an evaluation of long-term voiding diaries. Large voided volumes (functional capacity > 250 cc) or longer micturition intervals (> 2 h.), absence of nocturia or symptom-free periods reduce the likelihood of IC. Further exclusion diagnostics include urine tests (infection), cytology (in-situ carcinoma), ultrasound (calculi, bulks, anomalies) and urodynamics in selected cases. Bladder capacity measurements under sedoanalgesia are of limited value, since functional low-volume bladders can be mechanically extendable. Cystoscopy under general anesthesia represents the diagnostic standard procedure for IC during which 90% of IC-patients present with characteristic mucosal glomerulations after bladder distension. Biopsies are recommended for exclusion of malignancy. Potassium-leak testing plays no relevant role in routine diagnostics due to its poor sensitivity. Similarly, complex determinations of novel IC markers (histamine, tryptase, cytokines, growth factors, substance P, nitric oxide) are of no relevance in clinical settings and should be restricted to research projects.
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PMID:[Diagnosis of interstitial cystitis]. 1113 71

Chronic ulcerative colitis (CUC) is an inflammatory destructive disease of the large intestine characterized by motility and secretion disorders. In the past decade, attention has been paid to the role of neuronal structures and mast cells in regulating inflammatory and immune responses in inflammatory bowel disease (IBD). The present study was performed to demonstrate neuronal fibres (NF) and cells containing substance P (SP), tryptase and serotonin (SER) in the colonic wall of patients with CUC in remission. Biopsy specimens of 6 patients with CUC were investigated with immunocytochemical methods. Normal colon tissue obtained from 6 patients with rectal carcinoma was used as a control. An increased number of SP- and SER-positive NF was found in all the layers of the intestinal wall. The number of SER-containing endocrine cells in the mucosal glands was also increased per crypt. Tryptase-, SP- and SER-immunopositive mast cells were found in higher amounts than in control specimens in close apposition to the basal lamina of the glands among the epithelial cells and in other layers of the gut wall. Two types of mast cells were found: mast cells containing both tryptase and SP, and mast cells containing tryptase only. It is concluded that interactions between neuronal elements and mast cells play a significant role in the progress and maintenance of inflammatory processes in CUC.
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PMID:Mast cells and inflammatory mediators in chronic ulcerative colitis. 1208 39

The enteric nerve plexus in the colon was investigated in rats with chemically induced colonic adenocarcinoma. Tissue specimens from the colons of four group rats, namely controls, treated animals without development of colonic macro- or microscopic changes, rats with dysplasia and lymphoid hyperplasia, and rats with colonic adenocarcinoma were studied using immunocytochemistry, and quantified by computerized image analysis. No morphometeric changes were found in the treated rats regarding the myenteric and submucosal ganglia, with the exception of nitric oxide synthase (NOS), where the number of nerve cell bodies/ganglia was reduced in the myenteric ganglia in rats with both lymphoid hyperplasia and dysplasia, and carcinoma. The relative volume density of protein gene product (PGP) 9.5-immunoreactive (IR) nerve fibres was higher in the muscularis propria in rats with lymphoid hyperplasia and dysplasia, and carcinoma. However the relative volume density of PGP 9.5-IR nerve fibres was higher in the submucosa in rats with carcinoma only. The relative volume density of substance P- and VIP-IR nerve fibres was significantly higher in the muscularis propria in rats with colonic carcinoma. The relative volume density of NOS-IR nerve fibres was significantly decreased in both muscularis propria and submucosa in rats with lymphoid hyperplasia and dysplasia, and carcinoma. These findings imply that regulatory signals of the enteric innervation may be involved in the pathogenesis of colorectal cancer.
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PMID:Changes in the colonic enteric nervous system in rats with chemically induced colon dysplasia and carcinoma. 1254 27

Most patients suffering from breast carcinoma do not die due to the primary tumor but from the development of metastases. Active migration of cancer cells is a prerequisite for development of these metastases. We used time-lapse videomicroscopy and computer-assisted cell tracking of MDA-MB-468 human breast carcinoma cells, which were incorporated into a three-dimensional collagen matrix, in order to analyze the migratory activity of these cells in response to different neurotransmitters. Our results show that met-enkephalin, substance P, bombesin, dopamine, and norepinephrine have a stimulatory effect on the migration of the breast cancer cells; moreover, these cells show positive chemotaxis towards norepinephrine as was analyzed by the directionality and persistence on a single-cell basis. Gamma-aminobutyric acid (GABA) however has an inhibitory effect. Endorphin and leu-enkephalin, as well as histamin and acetylcholine, had no influence on the migratory activity of the cells. In summary, we provide evidence for a strong regulatory involvement of neurotransmitters in the regulation of breast cancer cell migration, which might provide the basis for the use of the pharmacological agonists and antagonists for the chemopreventive inhibition of metastasis development.
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PMID:Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells. 1288 99

The active migration of tumor cells, a crucial requirement for metastasis development and cancer progression, is regulated by signal substances including neurotransmitters. We investigated the migration of tumor cells within a three-dimensional collagen matrix using time-lapse videomicroscopy and computer-assisted analysis of the migration path. Tumor cell migration is induced by norepinephrine, dopamine and substance P. We show that this induced migration, using MDA-MB-468 breast and PC-3 prostate carcinoma cells, can be inhibited by using specific, clinically established receptor antagonists to the beta2-adrenoceptor, the D2 receptor, or the neurokinin-1 receptor, respectively. All of the investigated neurotransmitters significantly activated the cyclic adenosine-monophosphate response element binding protein (CREB). Furthermore, microarray analysis revealed changes of gene expression toward a highly motile tumor cell type, including an upregulation of the alpha2 integrin, which is an essential adhesion receptor for collagen in migration. The gene for the tumor suppressor gelsolin was downregulated. These 2 critical alterations were confirmed on the protein level by flow-cytometry and immunoblotting, respectively. Neurotransmitters thus induce a metastatogenic tumor cell type by directly regulating gene expression and increased migratory activity, which can be prevented by established neurotransmitter antagonists.
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PMID:Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. 1535 35


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