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 neuropeptide mediator of inflammation, was quantified during the evolution of trinitrobenzene sulfonic acid (TNBS)-induced ileitis in guinea pigs. Ileitis was induced by a single intraluminal injection of TNBS (30 mg/kg in 50% ethanol). Misoprostol, a prostaglandin E1 analogue, was administered parenterally (30 mg/kg sc twice daily) in a group of TNBS-treated animals. Control guinea pigs received intraluminal saline (sham) or 50% ethanol (TNBS vehicle). Guinea pigs were evaluated at day 1, 3, 7, 14, or 30 after ileitis induction for substance P content (radioimmunoassay) and distribution (immunohistochemistry), morphology, myeloperoxidase (MPO) activity, and protein leak into the gut lumen. TNBS administration caused an increase in ileal MPO activity that peaked at day 7 and increased mucosal leak of protein. Misoprostol attenuated the granulocyte infiltration (MPO) response to TNBS but exacerbated the mucosal leak of protein. Substance P levels in whole ileal segments were unaltered from baseline on day 1 in all groups. On day 3 a marked decrease in ileal substance P content was evident in the TNBS and TNBS + misoprostol groups. As early as day 1, immunohistochemistry suggested that the decreased substance P content was confined to the mucosa and submucosa, because myenteric plexus staining was not reduced. Loss of staining in the perivascular nerves was particularly marked. Substance P content and distribution returned to baseline by day 30 post-TNBS, although MPO activity remained slightly elevated. We concluded that TNBS ileitis is associated with a marked reduction in mucosal and submucosal substance P content in parallel with the inflammatory response. Although misoprostol attenuated granulocyte infiltration in this model, it did not prevent the disturbances in enteric substance P or mucosal protein leak.
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PMID:Substance P levels in experimental ileitis in guinea pigs: effects of misoprostol. 769 Jan 87

In vitro electrophysiological studies of ileal circular muscle from rabbits with ricin-induced inflammation were performed to investigate whether altered neural control or myogenic activity contributes to previously described changes in in vivo myoelectric activity. Ricin treatment increased mean slow-wave amplitude but not frequency or resting membrane potential. Prolonged electrical field stimulation evoked a hyperpolarization during the stimulus train and a depolarization on cessation of stimulation. In the presence of atropine, the depolarization was larger in ricin-treated tissue than in control tissue, showing that ileitis enhanced noncholinergic excitation. The nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester reduced the hyperpolarization in ricin-treated but not in control tissue, suggesting that inflammation increased nitric oxide-mediated inhibition. Substance P desensitization reduced noncholinergic excitation and mean slow-wave amplitude only in ricin-treated tissue, demonstrating that changes in these parameters during inflammation resulted from increased release of, or sensitivity to, tachykinins. These data suggest that acute ileitis alters tachykinin- and nitric oxide-mediated neurotransmission that may affect the normal pattern of ileal motility and/or sensory reflexes.
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PMID:Changes in enteric neural regulation of smooth muscle in a rabbit model of small intestinal inflammation. 776 66

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

Inflammatory bowel disease is associated with altered intestinal motility and epithelial damage. Hyperthermia induces heat shock protein expression, components of a basic cellular defence mechanism, and consequently prevents ischaemic damage. Here we investigate whether hyperthermia may prevent altered smooth muscle function as well as underlying inflammation in a model of inflammatory bowel disease. Ileal heat shock protein expression was induced in rats by hyperthermic shock (41.5 degrees C; 5 min). Two hours after heating or sham treatment, ileitis was evoked by TNBS. Ileal samples were taken 4 h later to determine the contractile response of circular muscle strips, and to measure heat shock protein expression, LTB4 generation and damage/inflammation. Ileitis was associated with an increase in the contractile response of circular muscle to substance P but not neurokinin A or nerve stimulation. Hyperthermia induced heat shock protein expression and also prevented this functional change as well as TNBS-induced LTB4 production, subsequent infiltration of neutrophils and epithelial damage. Thus, intestinal inflammation is associated with alterations in tachykinergic control of smooth muscle as well as inflammatory changes. Hyperthermia prevents these changes and induces heat shock protein expression. Pharmacological induction of these proteins may offer a novel clinical strategy in treating both of these aspects of disease.
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PMID:Hyperthermia prevents functional, histological and biochemical abnormalities induced during ileitis. 1008 37

Intraluminal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in ethanol is a classical model of colitis in the rat. Little is known about the time-related effect of TNBS on the contractility and morphology of the rat ileum. After 36 h, TNBS induced acute ileitis. Spontaneous activity of longitudinal muscle strips was decreased, as were receptor- and nonreceptor-mediated contractions and contractions induced by electrical stimulation. After 1 week, mucosal integrity was restored, although the thickness of both mucosal and muscle layers was increased. Spontaneous activity, receptor- and nonreceptor-mediated contractions and electrically induced contractions of longitudinal muscle strips were increased due to hypertrophy and hyperplasia of smooth muscle cells. This was confirmed in the contractility study of individual muscle cells. Functional alterations after 1 week were restricted to a decreased response to substance P. TNBS-ileitis in the rat lacks a chronic phase and is accompanied by functional hypocontractility of longitudinal smooth muscle cells during the acute inflammation, whereas the contractility of the longitudinal muscle layer is increased in the postinflammation phase due to structural alterations. There is a selective inhibition of the response to substance P in the postinflammation phase.
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PMID:Effect of TNBS-induced morphological changes on pharmacological contractility of the rat ileum. 1144 87

The efferent secretomotor activity of capsaicin-sensitive nerves was monitored during the evolution of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis in the guinea pig by recording changes in short-circuit current (DeltaI(sc)) in response to capsaicin, substance P (SP), and carbachol. Submucosal-mucosal preparations mounted in standard Ussing chambers were studied at time 0, at 8 h, and 1, 3, 5, 7, 14, and 30 days following the intraluminal instillation of TNBS or saline. Maximal DeltaI(sc) responses to capsaicin were dramatically attenuated (54%) by 24 h. By day 7, SP- and TTX-insensitive carbachol-stimulated DeltaI(sc) were also significantly reduced. Similar attenuation in capsaicin and carbachol responses was observed in jejunal tissue 20 cm proximal to the inflamed site at day 7. These studies demonstrate that efferent secretomotor function of capsaicin-sensitive nerves is maintained early in TNBS ileitis but significantly reduced by 24 h. By day 7, defects in enterocyte secretory function at inflamed and noninflamed sites also occurred, an effect that may be mediated by circulating cytokines.
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PMID:Alterations in capsaicin-evoked electrolyte transport during the evolution of guinea pig TNBS ileitis. 1201 22

To understand the interactions between substance P and gut inflammation, changes in substance P levels were evaluated in a chronic model of ileitis in response to three anti-inflammatory agents with distinct mechanisms of action. The agents were the prostaglandin E(1) analogue misoprostol (30 mug/kg, s.c., b.i.d.), the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mug/ml in drinking water) and the leumedin, N-(fluorenyl-9-methoxycarbonyl)-L-leucine (NPC 15199, 10 mg/kg, s.c.). Ileitis was induced by a transmural injection of trinitrobenzene sulphonic acid (TNBS 30 mg/kg in 50% ethanol) into the distal ileum of guinea-pigs. All anti-inflammatory therapies were introduced after TNBS administration and continued until day 7, when guinea-pigs were killed. Ileal substance P levels were measured by radioimmunoassay, and granulocyte infiltration was quantified by myeloperoxidase (MPO) activity. Protein and nitrite (an index of nitric oxide formation) levels in a luminal saline lavage were quantified in all groups. TNBS ileitis caused a marked reduction in ileal substance P content and increased MPO activity, protein and nitrite secretion. The nitric oxide synthase inhibitor, L-NAME, completely restored all parameters to baseline. Misoprostol attenuated the granulocyte infiltration and exacerbated protein leak but had no effect on substance P levels. In contrast, NPC 15199 had no effect on granulocyte infiltration but normalized substance P levels and protein leak. Only L-NAME and NPC 15199 blocked the TNBS induced increase in nitrite levels. These results suggest that the regulation of granulocyte infiltration in this model is unrelated to changes in substance P levels. Inhibition of nitric oxide synthase was the most effective therapeutic strategy in TNBS ileitis but the precise interactions between nitric oxide and the enteric nervous system during inflammatory states remain to be defined.
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PMID:Anti-inflammatory agents and substance P depletion in experimental ileitis. 1847 36

Nicotine is protective in ulcerative colitis but not Crohn's disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4.
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PMID:Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats. 2688 Nov 75