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)

Substance P, a neurotransmitter found in colonic mucosa, can alter gut immunologic, vascular, and motor phenomena. Thus, it may have an important role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD). By radioimmunoassay of the extracts of endoscopically obtained rectal mucosal biopsies in affected patients, we evaluated mucosal substance P levels. Non-inflammatory bowel disease patients undergoing lower endoscopies and biopsies served as controls. There were significantly increased concentrations of substance P in patients with UC, compared with controls (p < 0.05) and compared with patients with CD (p < 0.005). The mucosal levels in CD patients were significantly lower than in controls (p < 0.05). Patients with active rectal CD had lower levels than patients with no evidence of active rectal disease. For the CD and UC patients, there was a strongly positive correlation between rectal mucosal substance P concentrations and total histologic inflammation scores (r = 0.7, p = 0.001). A strong correlation existed for rectal mucosal substance P concentrations and mucosal mononuclear cell scores (r = 0.7, p = 0.001) and for rectal mucosal substance P concentrations and the combined scores of mucosal neutrophils and eosinophils (r = 0.7, p = 0.002). In conclusion, the rectal mucosal substance P concentrations in patients with UC and CD are significantly different. Thus, substance P may have a different role in the pathogenesis of each of these entities. It is possible that the elevated concentrations in patients with UC are contributing to the increased inflammation seen in these patients. Alternatively, measured mucosal substance P levels may simply reflect the end result of the different inflammatory processes in UC and CD, rather than the cause. It is possible that the inflammatory cells are contributing to the measured concentrations.
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PMID:Rectal substance P concentrations are increased in ulcerative colitis but not in Crohn's disease. 768 84

Regulatory neuropeptides are widely distributed in the gastrointestinal tract, where they play an important role in motility, secretion, and immune and inflammatory responses. In this study, the rectal mucosal content of somatostatin (SOM), substance P (SP), beta-endorphin (BE), and thyrotropin-releasing hormone (TRH) was measured by radioimmunoassay in 56 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), 15 patients with acute infectious colitis (AIC), and 11 controls, who showed no inflammation of the rectal mucosa, nor abnormal bowel movements. The content of immunoreactive (ir)-SOM was decreased in UC patients, especially in those with persistent disease activity, while the levels of ir-SP, BE, and TRH were increased in such patients. Some changes of ir-peptide levels were also observed in CD and AIC patients. The changes in neuropeptide levels were analyzed in relation to histological grades of inflammation in UC patients, grades 4-5 showing the most significant changes. The levels of ir-SOM, SP, BE, and TRH showed no significant change in chronic persistent UC when measured 6-12 months after the initial examination. In contrast, in patients with remitting intermittent UC, the levels of SP and BE decreased during remission. Abnormal intestinal neuropeptide content may be implicated in the continued mucosal immune and inflammatory responses that are manifested in patients with inflammatory bowel disease.
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PMID:Abnormal neuropeptide concentration in rectal mucosa of patients with inflammatory bowel disease. 884 73

Gastrointestinal (GI) disease is a common manifestation of HIV infection. Symptoms may result from the acquisition of intestinal infection, but in certain cases functional and mucosal abnormality may result from mucosal HIV infection. The pathogenesis of HIV enteropathy is poorly understood, but a range of neuroenteric disturbances has been described including a reduction in mucosal substance P (SP). Inflammatory bowel disease (IBD) is a generic term used to describe two major clinical entities; Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of mucosal neuropeptide expression has been implicated in the pathogenesis of CD and UC. Mucosal SP expression has been variously described as increased, normal or reduced in intestinal tissue from patients with IBD. In contrast, uniform increases in mucosal SP receptor (SPR) have been described in patients with IBD using quantitative autoradiography. The purpose of this study was to characterize intestinal mucosal SPR mRNA expression in control, HIV and IBD patients using semiquantitative reverse transcription PCR. Intestinal tissue was obtained during diagnostic colonoscopy from 7 control, 9 HIV-infected and 28 (12 CD and 16 UC) IBD patients. RNA was isolated from the tissue biopsies, reverse transcribed and amplified with primers specific for SPR. SPR mRNA expression was detected in 7/7 (100%) of control, 2/9 (22%) of HIV-infected, 12/12 (100%) of CD and 11/16 (69%) of UC intestinal biopsies. These data demonstrate that SPR mRNA expression is significantly reduced in patients with HIV infection. Reduced mucosal SPR expression may contribute to the mucosal abnormality, altered intestinal motility and GI symptoms associated with HIV infection.
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PMID:Mucosal substance P receptor expression in HIV infection and inflammatory bowel disease. 948 97

The chronic inflammatory bowel diseases (BID), Crohn's disease and ulcerative colitis, are characterized by recurrent periods of inflammation and tissue destruction. The clinical course is influenced by genetics, environmental factors, and the immune system. Recent insights (bench trials) benefiting from advances in genetic engineering and molecular biology have contributed to clinical care (bedside) in terms of actual or potential therapies. Does the neuroendocrine system significantly modify disease activity? Although conceptually appealing, evidence remains circumstantial. Compelling anecdotal reports exist that "stress" affects disease activity in terms of the frequency and severity of IBD flares (bedside), but the mechanisms underlying these observations are unknown. Evidence that neuroendocrine factors play a significant role in immunomodulation is progressing (bench). (i) Trinitrobenzene sulfonic acid (TNB)-induced colitis, although similar in unstressed Fisher and Lewis rats, shows marked worsening in stressed Lewis rats. (ii) Early studies of rectal pain perception suggest there are specific differences in neuroimaging studies (PET scans) in IBD patients compared to controls. (iii) Levels of substance P (SP) and its receptor are altered. (iv) Preliminary clinical studies with SP receptor antagonists show a trend toward improvement. (v) Importantly, the placebo response in clinical trials is as high as 45%. Evidence that neuroendocrine systems significantly modulate local inflammation is rapidly accumulating (bench), which will facilitate enhanced coordination of clinically relevant therapies (bedside).
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PMID:Neuroimmunomodulation in inflammatory bowel disease. How far from "bench" to "bedside"? 962 99

The distribution of and morphological changes in substance P containing nerve fibers were examined immunohistochemically in the colonic mucosa of ulcerative colitis (UC) patients. Quantitative and morphological changes in substance P fibers were analyzed by digitized morphometry. The linear density of substance P fibers was significantly greater in the UC group (19.4 +/- 1.2 microns/1000 micron 2) than in the Crohn's disease group (10.1 +/- 1.2 microns; P < 0.01) and the control group (8.4 +/- 0.8 microns; P < 0.01). Analysis of the UC group showed that the degree of inflammation affected the linear density of substance fibers, with "moderate" cases presenting the highest linear density and "severe" cases the lowest. Substance P fibers were thickened and coarse in UC; they were significantly wider in the UC group (2.5 +/- 0.5 microns) than in the Crohn's disease group (1.5 +/- 0.2 microns; P < 0.01) and the control group (1.2 +/- 0.1 microns; P < 0.01). In conclusion, alterations in substance P containing nerve fibers, as evidenced by both the linear density and morphology, may play some role in the pathogenesis of UC.
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PMID:Substance P containing nerve fibers in ulcerative colitis. 963 89

Different neuropeptide-containing nerve fibers were investigated to clarify their role in the pathogenesis of Crohn's disease (CD) using immunohisto- and immunocytochemical techniques. Specimens were obtained from patients with CD from grossly affected colonic regions, from biopsies obtained from patients with CD treated with mesalazine and from control individuals. Quantitative analysis was made for the changes of the number of nerve terminals and their vesicle contents. The distribution pattern of all immunoreactive (IR) nerve fibers was similar both in the control and in the surgical specimens as well as in the biopsies obtained. The number of the synapses, the IR nerve fibers and their vesicle content were markedly decreased in the grossly affected colonic regions. Some degenerated axons were found in close proximity to the plasma cells. Immunocytochemistry demonstrated that substance P, vasoactive intestinal polypeptide and somatostatin IR nerve fibers were in direct contact with the plasma cells, lymphocytes and other immunocompetent cells. The gap between the membranes of immunoreactive nerve terminals and immunocompetent cells was 20-200 nm, in a few cases even less. In the mesalazine-treated group the number of the IR nerve terminals as well as their vesicle content was increased. These results suggest that changes in the number of different neuropeptide-containing nerve terminals and their content might alter the neuroimmunological processes, because these peptides are known to be immunoregulators.
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PMID:Direct morphological evidence of neuroimmunomodulation in colonic mucosa of patients with Crohn's disease. 965 Aug 18

The role of nitric oxide in intestinal fluid and electrolyte secretion depends upon whether the conditions under study are physiological or pathophysiological. In physiological conditions, endogenous nitric oxide seems to be a proabsorptive molecule, based on the findings that nitric oxide synthase inhibitors reverse net fluid absorption to net secretion in mice, rats, guinea pigs, rabbits, and dogs. This proabsorptive mode involves the enteric nervous system, the suppression of prostaglandin formation, and the opening of basolateral K+ channels. However, in some pathophysiological states nitric oxide synthase may be produced at higher concentrations that are capable of evoking net secretion. Thus nitric oxide synthase contributes to the diarrheal response in trinitrobenzene sulfonic acid-induced ileitis in guinea pigs and is the mediator of the laxative action of several intestinal secretagogues including castor oil, phenolphthalein, bisacodyl, magnesium sulfate, bile salts, senna, and cascara in the rat. Corresponding with the in vivo results, nitric oxide-donating compounds or nitric oxide itself stimulate chloride secretion in the guinea pig and rat intestine in vitro. Exceptions are the diarrhea produced by bacterial enterotoxins in the rat, in which nitric oxide seems to have a proabsorptive role, and the mouse ileum in vitro, in which nitric oxide-donating compounds produce a net proabsorptive effect on basal ion transport. Several endogenous secretagogues (substance P, 5-hydroxytryptamine, interleukin-1beta), which are important mediators of the inflammatory bowel diseases, act, at least in part, through the liberation of nitric oxide. Clinical studies have shown that nitric oxide is elevated in several inflammatory bowel diseases and other secretory conditions including ulcerative colitis, Crohn's disease, toxic megacolon, diverticulitis, infectious gastroenteritis, and infantile methemoglobinemia. However, the determination of nitric oxide in secretory diarrhea per se does not give conclusive information on the nitric oxide contribution to clinical secretory diarrhea.
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PMID:Nitric oxide as a modulator of intestinal water and electrolyte transport. 972 40

Increasing evidence suggests that tachykinins are involved in the control of pathophysiological states, such as inflammation. The precise localization of tachykinin receptors is of paramount importance in the search for their possible physiological and pathological role; in this study, therefore, we attempted to define cellular sites of substance P (NK-1R) and neurokinin A (NK-2R) receptor expression in the healthy and the inflamed human intestine by in situ hybridization and immunohistochemistry. In the normal ileum and colon, NK-1R and NK-2R were localized to smooth muscle cells of the muscularis mucosae and propria and a few inflammatory cells of the lamina propria; NK-1R expression was also found in the muscular wall of submucosal blood vessels, enteric neurons and, to a lesser degree, in surface epithelial cells. Patients with Crohn's disease and ulcerative colitis showed a dramatic increase in NK-1R density relative to controls, in both the inflamed and the uninvolved mucosa. Up-regulation of NK-1R was particularly evident on epithelial cells lining the mucosal surface and crypts, as well as on endothelial cells of capillaries and venules. Also, a marked increase in NK-2R expression was found in both groups of patients on inflammatory cells of the lamina propria, especially eosinophils. Our findings demonstrate that in the normal human intestine NK-1R and NK-2R are expressed in multiple cell types, which are endowed with different physiological functions; in addition, they demonstrate that both NK-1R and NK-2R are up-regulated in patients with Crohn's disease and ulcerative colitis. Taken together, these observations may have important physiological and pathophysiological implications, and provide the rationale for the use of NK-1R and NK-2R antagonists in the treatment of inflammatory bowel disease.
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PMID:Substance P (neurokinin-1) and neurokinin A (neurokinin-2) receptor gene and protein expression in the healthy and inflamed human intestine. 1107 11

Knowledge of the neurochemical coding of submucosal neurones in the human gut is important to assess neuronal changes under pathological conditions. We therefore investigated transmitter colocalization patterns in rectal submucosal neurones in normal tissue (n=11) and in noninflamed tissue of Crohn's disease (CD) patients (n=17). Neurone-specific enolase (NSE), choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), substance P (SP), nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) were detected immunohistochemically in whole-mount preparations from rectal biopsies. The neuronal marker NSE revealed no differences in the number of cells per ganglion (controls 5.0; CD 5.1). Four cell populations with distinct neurochemical codes were identified. The sizes of the populations ChAT/VIP (58% vs. 55%), ChAT/SP (8% vs. 8%), and ChAT/- (22% vs. 22%) were similar in control and CD. The population VIP/- was significantly increased in CD (12% vs. 2% in controls). Unlike in controls, all NOS neurones colocalized ChAT in CD. Thickened CGRP-fibres occurred in CD. We identified neurochemically distinct populations in the human submucous plexus. The increase in the VIP/- population, extensive colocalization of ChAT and NOS and hypertrophied CGRP fibres indicated adaptive changes in the enteric nervous system in noninflamed rectum of CD patients.
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PMID:Neurotransmitter coding of enteric neurones in the submucous plexus is changed in non-inflamed rectum of patients with Crohn's disease. 1143 88

1. This in vitro study was designed to determine the potential use of the NK(1) antagonist, SR140333 as an anti-diarrhoeal treatment for food allergy or inflammatory bowel disease. The effect of various immune and neuronal stimuli on human colonic substance P (SP) release and the effect of SR140333 on subsequently stimulated mucosal ion transport was investigated. 2. Submucosal and sensory nerve fibre stimulation using electrical field stimulation (1 ms/7 Hz/7 V) and capsaicin (50 microM) respectively, mast cell activation by anti-IgE (1/250 dilution) and granulocyte stimulation using fMLP (50 microM) each released SP and evoked a secretory response. 3. SP and the NK(1) selective agonist, Sar-SP (0.1 - 1000 nM) stimulated an increase in colonic secretion which was antagonized by SR140333 (pD'(2)=6.7 and 7.25 versus SP and Sar-SP respectively). 4. SR140333, at a concentration that blocked NK(1)-mediated secretion (500 nM), also reduced the secretory response to both alphaIgE and capsaicin. This suggests a pathophysiologic role for NK(1) receptors. 5. Capsaicin evoked SP release was increased in tissue taken from Crohn's disease but not ulcerative colitis patients. The response to SP was however reduced by 70 and 89% respectively. 6. Mast cells and sensory afferents contribute to allergic diarrhoea. Since SR140333 reduced the secretory response to mast cell and afferent stimulation this compound may be particularly useful in reducing the symptoms of food allergy.
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PMID:Human colonic anti-secretory activity of the potent NK(1) antagonist, SR140333: assessment of potential anti-diarrhoeal activity in food allergy and inflammatory bowel disease. 1149 21


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