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)

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

The motility disorders in patients with slow-transit constipation have been attributed to a disturbance in the peptidergic innervation of the colonic enteric nervous system. The nature of this disturbance is, however, controversial. In the present study 7 patients with long-standing severe slow- transit constipation were included, and normal tissues from the colon of 6 patients, which had undergone colonectomy because of polyp, chronic diverticulitis, prolapsis and volvulus were used as controls. The concentrations of several neuroendocrine peptides were measured in tissue extracts by radioimmuno-assays. The level of pancreatic polypeptide was high in 2 patients and low in one patient. Peptide YY level was high in 3 patients and low in one patient, and that of neuropeptide Y was high in 4 patients. Somatostatin and vasoactive intestinal polypeptide levels were high in 3 patients and substance P concentration was low in 3 patients. Neurotensin level was high in one patient and low in another patient. Galanin concentration was low in 2 patients and high in one patient. Gastrin-releasing peptide level was high in one patient and that of enkephalin was high in 2 patients. All patients had altered concentrations of several neuroendocrine peptides except one, who had only a low level of galanin. It is concluded that patients with slow-transit constipation have disturbed neuroendocrine peptides in common, though the nature of this disturbance varies between patients and in most patients several neuroendocrine peptides were affected. This may explain the controversial results obtained in previous studies.
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PMID:Colonic neuroendocrine peptide levels in patients with chronic idiopathic slow transit constipation. 1005 11

Diverticulosis is largely asymptomatic but recent evidence suggests that episodes of acute diverticulitis double the risk of subsequently suffering from recurrent noninflammatory pain. Numerous animal models demonstrate how inflammation is followed by circular muscle hypertrophy, abnormalities of innervation, and increased sensitivity to cholinergic agents. There is also an impairment of norepinephrine and acetylcholine release and damage to nitrergic neurons. These changes are also associated with visceral hypersensitivity. Many of the features, including visceral hypersensitivity are also seen in symptomatic patients with diverticulosis. The trinitrobenzene sulfonic acid colitis model demonstrates that inflammation is followed by long lasting increases in tachykinin and other neuropeptide immunoreactivity. These changes occur both in the mucosa and myenteric plexus and parallel changes seen in resections and mucosal biopsies in diverticular patients. These neural abnormalities may be responsible for the visceral hypersensitivity, which explains why symptoms correlate poorly with objective abnormalities such as intraluminal pressure or motor patterns. Treatment of visceral hypersensitivity might be more effective than current therapies that often leave pain unaltered.
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PMID:How inflammation changes neuromuscular function and its relevance to symptoms in diverticular disease. 1688 93

Diverticulitis causes recurrent abdominal pain associated with increased mucosal expression of mucosal galanin and substance P (SP). We studied changes in mucosal and myenteric plexus neuropeptides in adult rats using a model of colonic inflammation, trinitrobenzenesulphonic acid colitis. We assessed the effects on the pan-neuronal markers protein gene product 9.5 (PGP9.5) and neurofilament protein, as well as specific neuropeptides at 1, 2, 3, 4, 6, 8, 10 and 14 weeks. Following the acute injury there was macroscopic resolution of inflammation but minor microscopic abnormalities persisted. Percent area stained of mucosal PGP9.5 fell initially but average levels on days 21 and 28 levels were significantly elevated (P < 0.001), returning to normal by day 42. Percent area staining of PGP9.5 in the muscle rose immediately and remained significantly elevated at 70 days (P < 0.001). SP, neuropeptide K and galanin followed a similar overall pattern. SP to PGP9.5 ratio was significantly increased in the muscle both acutely (days 1-28) and in the long term (days 70 and 98), whereas the galanin to PGP9.5 ratio was significantly increased in the mucosa throughout the study. Low-grade chronic inflammation after an acute initial insult causes a persistent increase in the expression of galanin in the mucosa and SP in muscle layer.
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PMID:Prolonged elevation of galanin and tachykinin expression in mucosal and myenteric enteric nerves in trinitrobenzene sulphonic acid colitis. 1820 79

Some patients with colonic diverticula suffer recurrent abdominal pain and exhibit visceral hypersensitivity, though the mechanism is unclear. Prior diverticulitis increases the risk of being symptomatic while experimental colitis in animals increases expression of neuropeptides within the enteric nervous system (ENS) which may mediate visceral hypersensitivity. Our aim was to determine the expression of neuropeptides within the ENS in diverticulitis (study 1) and in patients with symptomatic disease (study 2). Study 1 - Nerves in colonic resection specimens with either acute diverticulitis (AD, n = 16) or chronic diverticulitis (CD, n = 16) were assessed for neuropeptide expression recording % area staining with protein gene product (PGP9.5), substance P (SP), neuropeptide K (NPK), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and galanin. Study 2 - Seventeen symptomatic and 15 asymptomatic patients with colonic diverticula underwent flexible sigmoidoscopy and multiple peridiverticular mucosal biopsies. Study 1- Neural tissue, as assessed by PGP staining was increased to a similar degree in circular muscle in both AD and CD. The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Study 2 - Mucosal histology was normal and PGP9.5 staining was similar between groups however patients with symptomatic diverticular disease demonstrated significantly higher levels of SP, NPK, VIP, PACAP and galanin within the mucosal plexus. Patients with symptomatic diverticular disease exhibit increased neuropeptides in mucosal biopsies which may reflect resolved prior inflammation, as it parallels the changes seen in acute and chronic diverticulitis.
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PMID:Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms. 1945 15