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)

Seven patients (6 women, 1 man) with severe idiopathic chronic constipation, who underwent surgery with subtotal colectomy and ileorectal anastomosis, were investigated for the occurrence and density of nerve fibres, immunoreactive to different neuropeptides in the mucosa, submucosa, ganglia and smooth muscle in fresh specimens from the colon ascendens, the colon transversum and the colon descendens-sigmoideum. The following substances were studied: enkephalin, substance P, somatostatin, neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peptide, bombesin, motilin, tyrosine hydroxylase, dynorphin and galanin. Nerve fibres immunoreactive to CGRP occurred in large numbers in the myenteric ganglia of the patients with severe idiopathic chronic constipation, whereas in the myenteric ganglia of the control cases they only occurred in low numbers. In two patients there was no detectable motilin immunoreactivity and in one patient only sparse in the mucosa and the smooth muscle. The other neuropeptides investigated occurred in the density and distribution previously reported in the normal gut. With the present technique there were indications that patients with severe idiopathic chronic constipation have a significant difference in the occurrence of immunoreactive nerve fibres to CGRP and motilin compared to control patients.
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PMID:Slow transit chronic constipation (Arbuthnot Lane's disease). An immunohistochemical study of neuropeptide-containing nerves in resected specimens from the large bowel. 228 99

To investigate the reported association between idiopathic chronic constipation and morphologic abnormalities of enteric nerves, we measured the concentrations of six neuropeptides, vasoactive intestinal peptide, peptide histidine-methionine, substance P, methionine5-enkephalin, neuropeptide Y, and the bombesinlike intestinal peptides, in descending colon from 4 patients with idiopathic chronic constipation. Decreased concentrations of vasoactive intestinal peptide (707 +/- 112 ng/g wet tissue) and peptide histidine-methionine (543 +/- 58 ng/g) were found in the muscularis externa obtained from constipated patients compared with normal concentrations (40 patients) of vasoactive intestinal peptide (1199 +/- 47 ng/g) and peptide histidine-methionine (815 +/- 45 ng/g). Vasoactive intestinal peptide was identified by immunocytochemistry in nerve fibers within the circular smooth muscle layer of descending colon obtained from 6 control patients, but not in nerve fibers within the circular smooth muscle of descending colon obtained from 3 patients with idiopathic chronic constipation. By contrast, the distribution of immunoreactive met5-enkephalin was similar in normal descending colon and in descending colon obtained from patients with idiopathic chronic constipation. Decreased colonic concentrations of vasoactive intestinal peptide (a candidate nonadrenergic, noncholinergic inhibitory neurotransmitter) may be associated with diminution of inhibitory innervation of colonic circular smooth muscle in some patients with idiopathic chronic constipation.
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PMID:Idiopathic chronic constipation is associated with decreased colonic vasoactive intestinal peptide. 244 45

Substance-P content in rectal mucosa was determined by radioimmunoassay in 28 diabetic patients (17 with severe chronic constipation and 11 with normal bowel function), 24 non-diabetic patients with severe functional constipation, and 27 normal controls. Substance-P content (pg/mg) in the rectal mucosa of diabetics with normal bowel function was significantly higher than that of non-diabetic controls (p < 0.001). Substance-P content in the rectal mucosa of diabetics with constipation was more than double that of patients with non-diabetic functional constipation (p < 0.01) and lower than that of diabetics with normal bowel function (p < 0.0375). Diabetic patients (constipated and non-constipated) have higher substance-P content in the rectal mucosa than non-diabetics. Lower substance-P rectal mucosa content in constipated diabetic patients than in non-constipated diabetics supports a possible role of substance P in the pathogenesis of diabetic constipation.
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PMID:Substance P levels in the rectal mucosa of diabetic patients with normal bowel function and constipation. 767 22

After Hirschsprung's disease was ruled out for 25 children who had severe chronic constipation, the authors studied the distribution of immunoreactivity for substance P (SP) and vasoactive intestinal peptide (VIP) in the intestinal wall, using immunofluorescence. SP and VIP immunoreactivity identify excitatory and inhibitory nerve fibres, respectively. Full-thickness rectal biopsy specimens were unsatisfactory, so seromuscular biopsies of the caecum, transverse colon, and sigmoid colon were obtained (by laparoscopy and laparotomy; n = 10 patients). SP-immunoreactive fibres were markedly reduced in seven, with concomitant reduction of VIP-immunoreactive fibres in four. In two other patients, there was no obvious reduction in SP- or VIP-immunoreactive fibres. In a patient who subsequently was found to have multiple endocrine neoplasia type 2b, the myenteric plexus was markedly hyperplastic, with an increase in nerve cells and nerve fibres. VIP-immunoreactive fibres were increased, but SP-immunoreactive fibres were markedly decreased. Surgical options included proximal stoma, Malone operation, and subtotal colectomy with preservation of the rectum. Three children with subtotal colectomy have had improvement over short-term follow-up. The combination of seromuscular laparoscopic biopsies and immunofluorescence demonstration of neuropeptides may identify new variants of intestinal neuronal dysplasia than can be treated successfully with surgery.
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PMID:Intractable constipation with a decrease in substance P-immunoreactive fibres: is it a variant of intestinal neuronal dysplasia? 880 18

In children with severe chronic constipation, abnormal distribution of substance P (SP) and vasoactive intestinal peptide (VIP), which represent excitatory and inhibitory nerves, respectively, has been reported. The normal distribution of these neuropeptides, however, is not well known. The aim of this study was to determine the populations of SP- and VIP-immunoreactive nerve fibres in the circular muscle of the colon in children. Surgically resected specimens were collected from a 6-year-old girl with familial polyposis coli (total colon) and nine patients with anorectal malformations aged 0-4 years (sigmoid colon). Double-labelling immunofluorescence was employed using neuron-specific enolase (NSE) with SP and NSE with VIP to count the percentage of SP- or VIP-labelled nerve fibres. These specimens showed normal submucous and myenteric plexuses stained with NSE. The population of SP- immunoreactive fibres was 15%-21% throughout the colon, and VIP was 39% in the caecum and 63%-65% in the transverse, descending, and sigmoid colon. In the four neonatal specimens (day 1 to 4), the SP population was only 1%-6% and the VIP population was also low (22%-33%). After 3 weeks of age, the populations had stabilised at 18%-26% for SP and 52%-62% for VIP. SP-immunoreactive nerve fibres were scarce in the neonatal period, and showed a rapid increase by 3 weeks and a similar though less dramatic increase in VIP-immunoreactive fibres. VIP-immunoreactive fibres were fewer in the caecum that at other colonic levels, where they accounted for 60% of NSE-labelled fibres; the SP population, however, was comparable at all levels of the colon at about 20% of NSE-labelled fibres.
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PMID:Distributions of substance P- and VIP-immunoreactive nerve fibres in the colonic circular muscle in children. 988 Jul

The aim of our study was to further investigate the pathophysiological mechanism underlying idiopathic chronic constipation (ICC), a disorder of colonic motility. A possible alteration of excitatory and inhibitory neurotransmission and also the role of inhibitory neurotransmitters such as nitric oxide (NO), 5'-adenosine triphosphate (ATP), and vasoactive intestinal peptide (VIP) has been evaluated on preparations of distal colon from patients with or without ICC. The isometric tension was recorded from isolated circular muscle strips of both experimental groups during pharmacological and electrical field stimulation (EFS). The contractile response obtained by acetylcholine (ACh 20 microM), EFS (20 Hz, 20 V, 1 msec, pulse trains lasting 1 min) and substance P (SP 1 microM) was significantly lower in ICC than in control preparations. The effect of inhibitory nonadrenergic, noncholinergic innervation was evaluated using EFS at low frequencies (0.5-8 Hz), after cholinergic and sympathetic blockade with atropine (3 microM) and guanethidine (3 microM). The maximum relaxation value expressed as percentage of inhibition of SP-induced contraction was significantly higher in ICC than in control preparations (87+/-2.4 and 67+/-6.3, respectively; P<0.05). Experiments with substances that antagonize or reduce the effect of putative inhibitory mediators (VIP 6-28, apamin and N(G)-nitro-L-arginine) suggest that an alteration in NO and ATP release is present in ICC preparations. In particular at a higher inhibitory frequency NO-mediated relaxation is enhanced in ICC vs control, supporting the hypothesis that excessive NO production may be involved in pathophysiological mechanism of constipation.
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PMID:Cholinergic stimulation and nonadrenergic, noncholinergic relaxation of human colonic circular muscle in idiopathic chronic constipation. 988 5

Substance P content was determined by radioimmunoassay in rectal mucosa of 17 children with idiopathic constipation and 9 with normal bowel movements who were used as controls. In children with chronic idiopathic constipation, rectal mucosa substance P levels were lower than levels in the control group: 47.6 +/- 11 vs. 79.4 +/- 11 pg/mg net weight respectively (differences not statistically significant). Substance P levels in rectal mucosa of children with soiling (11/17) did not differ from those of chronically constipated children without soiling (46.0 +/- 16 vs. 50.5 +/- 19 pg/mg net weight). In children with constipation, substance P levels did not correlate either with age or duration of symptoms. Substance P levels in normal controls were similar to levels previously observed in non-constipated adults, whereas levels in constipated children were intermediate between levels observed in healthy subjects and levels in adults with chronic constipation. These findings may point to a motility derangement as a possible factor in the pathogenesis of chronic constipation in childhood.
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PMID:Substance P in rectal mucosa of children with chronic constipation. 1137 Jan 80

Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are intestinal disorders which disrupt normal colonic motility. Enteric tachykinins are well-recognised to play a role in the motor control of the gut, and increased colonic levels of substance P are seen in IBD, whereas decreased levels have been reported in ICC. In this investigation, we have characterised the tachykinin receptor population of normal human colonic circular smooth muscle and examined any changes that occur in IBD and ICC. The selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A(4-10), caused concentration-dependent contractions in healthy tissues; neither NK1 receptor-selective nor NK3 receptor-selective agonists were contractile. In diseased preparations also, only [beta-Ala8]neurokinin A(4-10) caused contractions with EC50 values similar to health. The maximum contractile responses (Emax), however, were significantly decreased in both forms of IBD but significantly increased in ICC. The muscarinic acetylcholine receptor agonist, carbachol, also caused contractions in diseased tissues, but EC50 and Emax values were not significantly different from health. The differential changes in contractility found in IBD and ICC are specific to NK2 receptors, and may reflect the altered levels of substance P or other tachykinins found in these intestinal disorders.
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PMID:Differential alterations in tachykinin NK2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation. 1138 76

Patients with chronic constipation that fails to respond to treatment remain a challenge for paediatricians and surgeons. Ongoing work in our institution suggests that a number of children with intractable symptoms have slow transit constipation, which has only been described recently in paediatrics. Common features of slow transit are: delayed passage of the first meconium stool beyond 24 h of age, symptoms of severe constipation within a year, or treatment-resistant 'encopresis' at 2-3 years, soft stools despite infrequent bowel actions, and delay in colonic transit on a transit study. A proportion of children with slow transit constipation have an abnormality of intestinal innervation associated with the dysfunctional colonic motility, recognized as intestinal neuronal dysplasia (IND). Intestinal neuronal dysplasia type B, the most common variant of IND, is defined on rectal biopsy by hyperplasia of the submucosal plexus. On laparoscopic colon muscle biopsy, many specimens show reduced numbers of excitatory substance P-immunoreactive nerve fibres in the circular muscle. Functional markers of the nerves allow new diagnostic criteria to be developed which may also allow a more rational approach to treatment. The aetiology remains obscure and the optimal management poorly defined, although subtotal colectomy, proximal colostomy or appendicostomy (for antegrade enemas) have been tried. Once the anatomy and physiology of the colon in children with slow colonic transit is better understood, we will have defined not only a new form of constipation, but also will be able to consider new therapies.
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PMID:Slow transit constipation in children. 1188 3