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 carcinoid syndrome, a common feature of small intestinal carcinoid tumors with liver metastases, includes flushing, diarrhea, bronchoconstriction, and right heart failure. The etiology of the carcinoid syndrome is not well understood, but serotonin seems to be involved in the diarrhea, whereas tachykinins may play a role in the flush reaction. In a double blind placebo-controlled study, we studied the effect of octreotide in 20 patients with midgut carcinoid tumors and liver metastases. A sc injection of 50 micrograms octreotide caused a significant (P less than 0.001) decrease in median plasma tachykinins and serum pancreatic polypeptide, GH, and insulin for up to 4 h. Administration of octreotide (50 micrograms, twice daily, sc) caused a 26% decrease in urinary 5-hydroxyindoleacetia acid excretion, but the number of flushing attacks or bowel movements did not change significantly. A typical flush was provoked by pentagastrin, and plasma tachykinin and serotonin levels were measured. The flush reaction was graded on a 10-point visual analog scale. Octreotide (50 micrograms, sc) given 45 min before flush stimulation prevented tachykinin release completely and significantly reduced the median flushing score from 8.5 to 2. Placebo administered in the same way did not prevent tachykinin release after pentagastrin administration. Thus, octreotide prevents pentagastrin-induced flushing and the related hormonal changes in patients with the carcinoid syndrome.
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PMID:The effects of octreotide on basal and stimulated hormone levels in patients with carcinoid syndrome. 246 45

Substance P content was determined by radioimmunoassay in colonic mucosa from 24 patients with chronic severe constipation, 16 with active ulcerative colitis, and 28 normal controls. In patients with chronic severe constipation, the mean concentration of substance P (19.9 +/- 8.2 pg/mg) was significantly lower than in normal subjects (71 +/- 18 pg/mg). In patients with ulcerative colitis, colonic substance P concentration in inflamed mucosa (170 +/- 46 pg/mg) was significantly higher than its levels in normal subjects. Substance P may therefore have a role in the pathogenesis of clinical conditions associated with diarrhea and constipation.
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PMID:Colonic substance P levels are increased in ulcerative colitis and decreased in chronic severe constipation. 246 61

Nonadrenergic, noncholinergic (NANC) innervation, the third division of the autonomic nervous system, has both inhibitory and excitatory parts. The excitatory part received only limited attention. Substance P has been suggested to be the neurotransmitter of the excitatory part. The NANC-inhibitory innervation has recently been studied in detail. Although the neurotransmitter has not been conclusively identified, a substantial body of evidence exists to support vasoactive intestinal peptide (VIP) as the neurotransmitter. VIP is widely distributed in the body. Reports show that this innervation in animals and man plays a significant role in both health and disease. Pathological conditions could result from either an increase or decrease in VIP production. An absence of VIP-producing neurons has been identified to be responsible for Hirschsprung's disease in the alimentary system and hyperactive airways in the respiratory system. An increase in VIP production is associated with chronic water diarrhea syndrome in humans. Taking these factors into consideration, various therapeutic measures are suggested with the use of VIP or its antagonists.
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PMID:Vasoactive intestinal peptide (VIP), a putative neurotransmitter of nonadrenergic, noncholinergic (NANC) inhibitory innervation and its relevance to therapy. 256 97

Watery diarrhoea as distinct from dysentery is occasionally seen in intestinal amoebiasis, suggesting a component of intestinal secretion. To study the pathogenesis of this watery diarrhoea, we evaluated the effect of lysates of Entamoeba histolytica on active intestinal electrolyte transport using rabbit ileum and rat colon studied by the Ussing chamber-voltage clamp technique. Amoebic lysates added to the ileal and colonic mucosal surfaces did not alter electrolyte transport; in contrast, addition to the ideal and colonic serosal surfaces caused an increase in short-circuit current which was transient in the ileum but more prolonged in the colon. This increase in current corresponded to inhibition of active Na+ and Cl- absorption and apparent stimulation of Cl- secretion in rat colon. In rabbit ileum, the short-circuit current response was: (1) dependent on serosal Ca2+, (2) inhibited by serosally applied verapamil, (3) associated with reversible desensitization, and (4) only partially inhibited by heating. These characteristics were similar to those of a series of neurohumoral substances present in mammalian intestinal mucosa which affect active electrolyte transport by increasing the permeability of the basolateral membrane to Ca2+. Substances with these properties identified include serotonin, substance P and neurotensin. All three substances were shown to be present in amoebic lysates by radioimmunoassay. Serotonin was also present by high performance liquid chromatography (HPLC) and thin layer chromatography, and neurotensin by HPLC. Prostaglandins were not present by radioimmunoassay. Attempts were made to determine which of these neurohumoral substances contributed to the changes in intestinal transport caused by amoebic lysates. Serotonin was thought to be involved, from the inhibition of the transport effect of amoebic lysate on rat colon by anti-serotonin antibody and by bufotenine, which inhibits the effect of serotonin on ion transport. Prostaglandins also appeared to be involved, since pretreatment with PGE2 or indomethacin inhibited the effects of amoebic lysate on transport. We conclude that amoebae contain neurohumoral substances, including serotonin, neurotensin and substance P, which may be important in the intestinal secretion caused by amoebae. Serotonin appears partially responsible for the intestinal secretion. In addition, amoebae may induce prostaglandin synthesis by the intestinal mucosa which could also contribute to the secretory response. The relation between the neurohumoral substances which act by Ca2+ and the prostaglandins presumably caused to be synthesized in the intestinal mucosa is not known.
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PMID:Secretory hormones of Entamoeba histolytica. 286 Oct 68

The effects of various biologically active peptides on net jejunal water and electrolyte fluxes were studied in dogs in vivo. Vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), glucagon, gastrin, bombesin and neurotensin all had secretagogue activity, while methionine enkephalin stimulated net absorption. Somatostatin had no effect on net basal water and electrolyte transport, but inhibited glucagon-stimulated secretion. Secretin, calcitonin, substance P and pancreatic polypeptide (PP) did not have any effect on net water and electrolyte transport in the doses used in these experiments. The precise role played by these peptides in the control of intestinal transport has still to be determined. Studies in man have confirmed that food in the proximal small bowel stimulates secretion at sites remote from the application of food, and abnormal secretion of some peptides (e.g. VIP) has been associated with diarrhoea. Somatostatin has been used successfully to reduce the volume of certain types of secretory diarrhoea. Methods used in these experiments have been applied to the study of the composition and absorption characteristics of solutions used for oral rehydration in diarrhoea and in exercise-induced dehydration. Glucose polymers have been shown to be absorbed as rapidly as glucose from the jejunum.
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PMID:The effect of luminal and hormonal factors on small intestinal water and electrolyte transport. 287 15

A 65-year-old woman presenting with back pain, difficulties in walking and watery diarrhea. A right adrenal tumor and high excretion of catecholamines were found. Laboratory examinations showed raised levels of vasoactive intestinal polypeptide, pancreatic polypeptide, gastrin and calcitonin. Histology showed a combined pheochromocytoma-ganglioneuroma. The neoplastic cell population was immunohistochemically shown to contain tyrosine hydroxylase, neuropeptide Y, met-enkephalin, substance P, vasoactive intestinal polypeptide, calcitonin and calcitonin gene-related peptide. Postoperatively, the patient recovered fully and the hormone levels returned to normal.
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PMID:Adrenal pheochromocytoma-ganglioneuroma producing catecholamines and various neuropeptides. 318 92

Intubation techniques and scintigraphic studies were used to determine the origin and mechanism of diarrhoea in a patient with medullary thyroid carcinoma, high plasma immunoreactive calcitonin and normal circulating serotonin, substance P and prostaglandins E2 and F2 alpha. Normal function of the small intestine was found for the following: (a) absorption tests; (b) water and electrolyte absorption in the proximal jejunum; (c) 24 hour flow rate and composition of fluid entering the colon and (d) gastric emptying rate and small intestinal progression of a normal meal. By contrast, colonic function was markedly impaired in three ways: (a) water absorption was decreased by half; (b) as the main excreted solutes were organic acids, a large electrolyte gap was recorded in faecal water, and (c) colonic transit time of the meal marker was very short, and was in agreement with the rapid transit of ingested radioopaque markers. These data strongly suggest that decreased absorption in the colon secondary to a motor disturbance is the main mechanism of diarrhoea in this case of medullary thyroid carcinoma, while calcitonin induced small intestinal fluid secretion suggested earlier is either non-existent, or only of minor importance.
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PMID:Pathophysiological study of diarrhoea in a patient with medullary thyroid carcinoma. Evidence against a secretory mechanism and for the role of shortened colonic transit time. 337 22

In 16 consecutive patients with systemic mastocytosis, we prospectively evaluated a variety of gastrointestinal functions and examined how they relate to the occurrence of gastrointestinal symptoms. Nine patients had either a duodenal ulcer or duodenitis. Hypersecretion of gastric acid was present in 6 patients, and in these patients the mean basal acid output was 20.7 +/- 4.1 mEq/h (range 14-39 mEq/h). Impaired small intestinal absorption occurred in 5 patients, although this was usually mild. The mean fractional emptying rate of liquids for all patients (14.7% +/- 2.3% per minute) did not differ from that for controls (10.7% +/- 0.6% per minute). Mean mouth-to-cecum transit time measured by breath hydrogen testing was the same among patients (87.7 +/- 6.7 min) and controls (86.7 +/- 8.0 min). Plasma histamine concentrations were increased in all patients (mean 1886 pg/ml, range 480-7450) and correlated with the basal acid output (r = 0.64, p less than 0.02) but not maximal acid output or the presence or absence of pain or diarrhea. Mean fasting plasma concentrations of motilin, substance P, and neurotensin from 6 patients did not differ significantly from controls, whereas gastrin and vasoactive intestinal peptide were significantly less than in controls (p less than 0.01). Gastrointestinal symptoms, consisting of abdominal pain or diarrhea, occurred in 80% of patients. Abdominal pain classified as dyspeptic was usually associated with acid-peptic disease of the duodenum and hypersecretion of gastric acid, whereas abdominal pain of a nondyspeptic character was not. Only in those cases of diarrhea consisting of greater than 200 g stool/day was gastric acid hypersecretion frequently found. Neither fecal urgency nor nondyspeptic pain could be accounted for by alterations of gastrointestinal transit. These results demonstrate that gastrointestinal symptoms, peptic disease, and mild malabsorption are much more common than described previously in patients with systemic mastocytosis. Furthermore, the results provide no evidence for the contention that altered gastrointestinal transit is involved in the pathogenesis of these symptoms.
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PMID:Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. 339 14

Radioimmunoassays based on antisera raised against the tachykinins eledoisin (antiserum E7) and kassinin (antiserum K12) were used to measure the concentration of tachykinin-like immunoreactivity (TKLI) in plasma from 52 healthy subjects. 65 patients with carcinoid tumors (of which 46 had symptoms of both flushing and diarrhoea), and 6 patients with endocrine pancreatic tumors. The antisera did not crossreact with substance P (SP). Elevated concentrations of TKLI, as compared with healthy subjects, were found in 75% of the carcinoid patients, but in none of the patients with pancreatic tumors. Tumor metastases from 8 of the carcinoid patients all contained TKLI. Ion-exchange chromatography of plasma samples and tumor tissue extracts indicated the presence of several immunoreactive molecular forms. The elution patterns of the immunoreactivity detected by antisera E7 and K12 were similar, indicating that the same molecular species are measured by these antisera. None of the components coeluted with synthetic SP. One of the immunoreactive components in carcinoid tumor extracts coeluted with synthetic NKA. The major immunoreactive components in plasma from the patients eluted in a position different from that of all currently known mammalian tachykinins. Tachykinin immunoreactive material detected in tumor tissue and plasma of patients with carcinoid tumor may play a role in the symptomatology of the carcinoid syndrome.
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PMID:Antisera raised against eledoisin and kassinin detect elevated levels of immunoreactive material in plasma and tumor tissues from patients with carcinoid tumors. 608 59

A 55-year-old woman with an ovarian carcinoid presented with intermittent facial and cervical flushing for 10 years, watery diarrhea for 4 years, and abdominal pain without hepatomegaly. Markedly elevated systemic venous and arterial serotonin levels (830 ng/ml; nl = 50-200 ng/ml) were found. The highest serotonin levels were observed in the superior vena caval system, but serotonin as a marker for tumor localization was inaccurate and led to an unproductive neck exploration. The histological pattern of this tumor contained purely insular elements. No hepatic or nodal metastases were identified and the lesion was unilateral. Substance P levels were elevated in the venous drainage of the left ovary and in retrospect correctly localized the ovarian tumor. This peptide may prove to be another carcinoid tumor marker in addition to serotonin and 5-hydroxyindoleacetic acid. Substance P may also be an important mediator of symptoms in patients with carcinoid syndrome.
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PMID:Substance P in the localization of a carcinoid tumor. 620 86


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