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)

Filiform polyposis (FP) is a rare condition of uncertain pathogenesis, 28 cases of which have been published since it was first described in 1965. It is usually found in association with chronic inflammatory bowel disease, especially Crohn's disease and ulcerative colitis. The condition is characterized by the presence of numerous, densely packed, filiform polyps in the colon, which may resemble villous adenomas on endoscopy. We describe a case of FP occurring in a 33-year-old man with a 5-year history of Crohn's disease, in whom subtotal colectomy was performed because of perforation of the sigmoid colon. Microscopy revealed inflammatory pseudopolyps covered by largely normal and non-dysplastic colonic epithelium. The neuroendocrine system of the intestine in FP was investigated for the first time in this case: marked hyperplasia of endocrine cells immunoreactive for serotonin, somatostatin and enteroglucagon and of neural structures immunoreactive for substance P and vasoactive intestinal peptide was noted in the polyps and the adjacent intestinal mucosa. The patient has experienced no further complications in the 12 months since the operation. Medication administered in FP depends mainly on the nature of the underlying disease, and the amount of information published about this condition is as yet insufficient to allow any one specific type of treatment to be recommended. FP alone is not an indication for bowel resection but complications, such as massive haemorrhage or intestinal obstruction, may necessitate surgical intervention.
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PMID:Filiform polyposis: a case report describing clinical, morphological, and immunohistochemical findings. 139 19

1. Neurokinin A (NKA) is a mammalian tachykinin distributed principally in the nervous system, including the myenteric innervation of the gut. 2. NKA may be involved in neurogenic inflammation and as a modulatory factor in the diarrhoea associated with mucosal inflammation of inflammatory bowel disease (ulcerative colitis). 3. We evaluated the effect of NKA on the short-circuit current ISC, assumed to reflect electrogenic chloride secretion, across muscle-stripped rat colonic mucosa mounted in Ussing chambers. 4. Serosal addition of NKA produced a concentration-dependent (0.1-100 nM) increase in ISC with an EC50 (half-maximal effective concentration) value of 7.5 nM. The maximum (mean +/- S.E.M.) increase in ISC (microA/cm2) for NKA was 111 +/- 10. 5. Tetrodotoxin (0.5 microM) and bumetanide (10 microM), but not atropine (1.0 microM), hexamethonium (100 microM) or pyrilamine (10 microM), significantly inhibited NKA-induced increases in ISC. 6. The response to NKA was attenuated by 45 min pre-treatment with antisera raised against vasoactive intestinal polypeptide (VIP). Moreover, prior desensitization to VIP attenuated the effect of NKA. 7. These studies suggest that NKA increases ISC in rat colon, in part, through a non-cholinergic neural mechanism involving VIP.
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PMID:Neurokinin A increases short-circuit current across rat colonic mucosa: a role for vasoactive intestinal polypeptide. 165 54

Substance P (SP) is one of the endogenous tachykinin peptides implicated in neurogenic inflammation and may be critically involved in diseases as diverse as asthma, arthritis and inflammatory bowel disease. The current study was initiated to identify a rich source of SP receptor that would be amenable for studying the regulatory mechanism of the receptor. By using a radioligand receptor binding technique, sheep ileal smooth muscle membranes showed a much higher density of [3H]SP specific binding than other non-neural rat or sheep tissues and organs surveyed. Of the protease inhibitors tested, only phosphoramidon, a specific and potent enkephalinase inhibitor, prevented the degradation of [3H]SP and enhanced [3H]SP binding to the membrane. [3H]SP binding to the specific binding sites in the membranes was time-dependent and reached a steady state after 60 min at 22 degrees C in 25 mM Tris.NH3 (pH 7.4). Calcium and magnesium ions enhanced [3H]SP specific binding. Saturation binding studies showed that the dissociation constant (KD) and the density of maximum binding sites for [3H]SP specific binding were 0.54 nM and 83 fmol/mg of protein, respectively. The specificity of the [3H]SP labeled sites was SP greater than (4-11) SP greater than eledoisin greater than spantide greater than neurokinin-A greater than D-Pro2D-Phe7D-Trp9-SP. Neurokinin-B and senktide showed no inhibition of [3H]SP binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification and characterization of the substance P receptor in sheep intestinal smooth muscle membranes. 169 67

Neurogenic inflammation is a reaction which includes vasodilation, plasma extravasation, and smooth muscle contraction elicited by activation of and release of mediators from unmyelinated afferent nerve endings. Further release of inflammatory mediators follows activation of axon collaterals associated with these afferent nerve endings as axon reflexes. Substance P, somatostatin, vasoactive intestinal polypeptide, and calcitonin gene-related peptide are candidate mediators. Recent evidence suggests that several of these peptides may be colocalized either with one or more other peptides or with acetylcholine or noradrenalin. Communicating pathways exist between nerves within the mucosa and the muscle layers. Both long and short visceral reflexes occur. Inflammatory, mechanical, or chemical stimuli reaching the mucosa may release peptides from peripheral nerve endings. Thus neurogenic inflammation may be an important factor in inflammatory bowel disease.
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PMID:Neuropeptides, inflammation, and motility. 244 99

The mammalian tachykinins, substance P, substance K (neurokinin A) and neuromedin K (neurokinin B), are putative peptide neurotransmitters in both the brain and peripheral tissues. We used quantitative receptor autoradiography to localize and quantify the distribution of binding sites for radiolabeled substance P, substance K and neuromedin K in the canine gastrointestinal tract. Substance P binding sites were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, neurons in the myenteric plexus, mucosal epithelial cells, exocrine cells and lymph nodules. Substance K binding sites were distributed in a pattern distinct from substance P binding sites and were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, and neurons of the myenteric plexus. Neuromedin K binding sites were not observed in any area of the canine gastrointestinal tract although they were localized with high specific/non-specific binding ratios in the canine spinal cord. These results indicate that there are at least two distinct types of tachykinin receptor binding sites in the canine gastrointestinal tract, one of which probably recognizes substance P and the other substance K as endogenous ligands. In correlation with previous physiological data, these substance P and substance K receptor binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including gastric motility, mucosal ion transport, hemodynamics, digestive enzyme secretion and neuronal excitability. In addition these results demonstrate that receptor binding sites for substance P and substance K are expressed by cells involved in mediating inflammatory and immune responses. These data, together with our studies on surgical specimens from patients with inflammatory bowel disease, suggest that in a pathophysiological state tachykinins and their receptors may play a role in inflammatory bowel disease and should permit a rational approach to designing neuropeptide antagonists which may prove effective in treating inflammatory diseases.
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PMID:Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease. 245 86

The neuropeptide substance P modulates the activities of a number of different leukocytes that characterize both acute and delayed inflammatory responses. Substance P may play a role in the pathogenesis of such diverse diseases as arthritis, asthma, and inflammatory bowel disease.
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PMID:Neuropeptides and inflammation: the role of substance P. 247 50

Several lines of evidence indicate that tachykinin neuropeptides [substance P (SP), substance K (SK), and neuromedin K (NK)] play a role in regulating the inflammatory and immune responses. To test this hypothesis in a human inflammatory disease, quantitative receptor autoradiography was used to examine possible abnormalities in tachykinin binding sites in surgical specimens from patients with inflammatory bowel disease. Surgical specimens of colon were obtained from patients with ulcerative colitis (n = 4) and Crohn disease (n = 4). Normal tissue was obtained from uninvolved areas of extensive resections for carcinoma (n = 6). In all cases, specimens were obtained less than 5 min after removal to minimize influences associated with degradation artifacts and were processed for quantitative receptor autoradiography by using 125I-labeled Bolton-Hunter conjugates of NK, SK, and SP. In the normal colon a low concentration of SP receptor binding sites is expressed by submucosal arterioles and venules and a moderate concentration is expressed by the external circular muscle, whereas SK receptor binding sites are expressed in low concentrations by the external circular and longitudinal muscle. In contrast, specific NK binding sites were not observed in any area of the human colon. In colon tissue obtained from ulcerative colitis and Crohn disease patients, however, very high concentrations of SP receptor binding sites are expressed by arterioles and venules located in the submucosa, muscularis mucosa, external circular muscle, external longitudinal muscle, and serosa. In addition, very high concentrations of SP receptor binding sites are expressed within the germinal center of lymph nodules, whereas the concentrations of SP and SK binding sites expressed by the external muscle layers are not altered significantly. These results demonstrate that receptor binding sites for SP, but not SK or NK, are ectopically expressed in high concentrations (1000-2000 times normal) by cells involved in mediating inflammatory and immune responses. These data suggest that SP may be involved in the pathophysiology of inflammatory bowel disease and might provide some insight into the interaction between the nervous system and the regulation of inflammation and the immune response in human inflammatory disease.
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PMID:Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease. 283 38

The purpose of this study was to show if inflammatory cells within healthy or diseased human intestinal mucosa produce some regulatory neuropeptides. First, inflammatory cells were isolated from the intestinal lamina propria of 11 patients with ulcerative colitis or Crohn's disease. Also collected were cells from anatomically normal intestine derived from five patients requiring bowel resection for diseases not related to inflammatory bowel disease. Extracts of these isolated cells contained authentic substance P (SP) and vasoactive intestinal peptide (VIP) as shown by RIA and their elution profiles on HPLC. Immunostaining of cells from nine of 13 additional patients localized immunoreactive SP and VIP to secretory granules within most mucosal eosinophils. No other cell types stained positive. Messenger RNA encoding SP and VIP was localized to lamina propria eosinophils by in situ hybridization. Mucosa inflammatory cells, from eight of nine more patients, cultured in vitro, released detectable amounts of VIP, but not SP. It is concluded that intestinal eosinophils produce SP and VIP. Since the eosinophils store and release more VIP than SP, it is possible that VIP is the preferred secretory product.
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PMID:Eosinophils within the healthy or inflamed human intestine produce substance P and vasoactive intestinal peptide. 751 1

The distribution abnormality of vasoactive intestinal polypeptide-containing nerves (VIP-nerves) and substance P-containing nerves (SP-nerves) was immunohistochemically investigated in the colonic mucosa with inflammatory bowel disease (IBD) in relation to colonic glands and blood vessels in the lamina propria. In active ulcerative colitis (UC), VIP- and SP-nerves decreased in severe inflammatory lesions. VIP-nerves were almost absent particularly around crypt abscesses. Even in resolving and quiescent UC, VIP-nerves still decreased, depending on the decrease of glands and blood vessels. On the other hand, both nerves increased in some hypervascular lesions. In the uninvolved mucosa of UC, they did not change their distribution. In Crohn's disease, the distribution abnormality of both nerves resembled that of UC. These results suggest that the changes in VIP- and SP-nerve distributions in the mucosa with IBD are subsequent to mucosal inflammation and damage. However, these peptides are known to be immunoregulators, and their distribution abnormalities may induce the disorder of immunoregulation in the IBD mucosa and cause the mucosal damage and/or chronicity.
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PMID:Changes in neuropeptide-containing nerves in human colonic mucosa with inflammatory bowel disease. 752 53

Previous reports have described the ectopic expression of substance P binding sites on lymphoid aggregates and small blood vessels in inflammatory bowel disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345, RP-67,580, and L-703,606 abolished saturable 125I-Bolton-Hunter substance P binding to the ectopically expressed receptors in frozen sections of surgically resected bowel from five patients with either Crohn's disease or ulcerative colitis. The rank order of affinity was approximately substance P approximately CP-96,345 approximately L-703,606 > RP-67,580. These results suggest that: (i) the ectopically expressed substance P binding sites in inflammatory bowel disease are authentic NK-1 receptors, (ii) all ectopically expressed receptors on small blood vessels, and lymphoid aggregates as well as normally expressed receptors on the bowel circular muscle have similar receptor affinities and specificities for substance P and the non-peptide antagonists, and (iii) non-peptide antagonists may be therapeutically beneficial in inflammatory bowel disease by inhibiting the pro-inflammatory effects of substance P acting via the NK-1 receptor.
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PMID:Substance P binding sites on intestinal lymphoid aggregates and blood vessels in inflammatory bowel disease correspond to authentic NK-1 receptors. 752 13


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