Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The total cellular mass of the small intestine is well controlled and can adapt, with hypo- or hyperplasia, to a wide variety of stimuli. Luminal nutrients, hormonal factors and pancreatic and biliary secretions have all been implicated in the regulation of intestinal mucosal growth. The polyamines (putrescine, spermidine and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase. ODC) are critical for many cell growth processes and appear to play important roles in intestinal growth. During intestinal adaptation in response to jejunectomy, lactation. pancreatic-biliary diversion, starvation-refeeding and feeding with kidney bean lectin, intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis. With administration of the specific inhibitor of ODC (difluoromethylornithine, DFMO) the increase in ODC and polyamines is inhibited and intestinal growth is suppressed. In addition, the oral administration of exogenous polyamines results in precocious maturation of the neonatal rat intestine. These results suggest that the polyamines are important for intestinal growth.
 ...
PMID:Polyamines in intestinal growth. 208 16

Luminal and basolateral uptake of polyamines by the rat small intestine was studied in vivo. In the concentration range studied (0.1-5 mg per rat) 23-47% of the individual polyamines given intragastrically were found in the body after 1 h, with the small intestine retaining 4-12% of the dose. With spermidine or spermine, labelled polyamines accounted for 85-96% of the counts in the small intestine and between 72-82% were in the form given. However, with putrescine only 29-39% of the label found in the tissue remained in polyamine form and even less, 11-15%, as putrescine. Luminal uptake of polyamines was linear, non-saturable and was not stimulated when small intestinal growth was stimulated by phytohaemagglutinin (PHA). On the basolateral side of the gut, polyamine uptake was stimulated by PHA in a time-dependent way in advance of detectable growth. Overall polyamine recoveries were high (89-99%) with intraperitoneally administered spermidine and spermine. Moreover, a large proportion of the counts in the tissue (63-89%) were still in the original form. Even with putrescine, total recoveries of polyamines (72-88%) and putrescine (24-33%) were elevated in comparison with those from the lumen. Treatment of rats with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, reduced tissue polyamine content, although it had slight effects only on basolateral polyamine transport. The PHA-stimulated increase of polyamine uptake was not abolished in the presence of DFMO.
 ...
PMID:Luminal and basolateral polyamine uptake by rat small intestine stimulated to grow by Phaseolus vulgaris lectin phytohaemagglutinin in vivo. 210 37

The intestinal mucosa is a rapidly proliferative tissue, with a highly dynamic cell population. Its total cellular mass is well controlled and can adapt, with hypo- or hyperplasia, to a wide variety of stimuli. Luminal nutrients, hormonal factors, and pancreatic and biliary secretions have all been implicated in the regulation of intestinal mucosal adaptation. Similarly, the same factors appear essential for the maintenance of exocrine pancreatic structure and function. The polyamines (putrescine, spermidine, and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase, ODC) are important for many cell growth processes, and may play important roles in intestinal and pancreatic adaptation. During intestinal adaptation in response to jejunectomy, lactation and pancreatico-biliary diversion (PBD), intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis. With administration of the specific inhibitor of ODC (difluoromethylornithine, DFMO) the increases in ODC and polyamines are suppressed, and intestinal adaptation is abrogated. In pancreatic hyperplasia induced by caerulein, pancreatic polyamines are increased. With DFMO administration, caerulein-induced increases in pancreatic DNA synthesis were inhibited and pancreatic hypertrophy was partially suppressed. PBD-induced pancreatic hypertrophy, however, was not affected by DFMO. Thus, the role of polyamines in the adaptation of the pancreas, with a relatively quiescent proliferative status, is as yet undefined. It seems clear, however, that the induction of ODC and the resultant increase in polyamine biosynthesis are critical for the normal growth and especially for adaptive hyperplasia of the intestinal mucosa.
 ...
PMID:Polyamines in intestinal and pancreatic adaptation. 312 57

The evidence for and against an enteropancreatic trophic axis is reviewed. Luminal nutrition is essential for the maintenance of normal intestinal mucosal, and exocrine pancreatic, structure and function. Exclusion of luminal nutrition leads to mucosal hypoplasia and hypofunction with similar changes in the pancreas. The trophic effect of luminal nutrition may be mediated through the release of regulatory peptides with endocrine or paracrine effects. Enteroglucagon is the strongest candidate for the role of 'enterotrophin' while cholecystokinin (CCK) markedly influences pancreatic growth. Thus, CCK not only stimulates exocrine pancreatic secretion but makes acinar cells divide and the pancreas grow. The cellular mechanisms whereby trophic peptides influence normal and adaptive growth are also discussed with emphasis on polyamines (putrescine, spermidine and spermine) and the key enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO). When polyamine synthesis is blocked with the ODC inhibitor, difluoromethyl ornithine (DFMO), the adaptive intestinal hyperplasia of pancreatico-biliary diversion is either inhibited or completely prevented. A proposed sequence of events might be as follows: luminal nutrients, particularly long-chain fats, reach the ileum and colon and stimulate increased enteroglucagon release. Enteroglucagon binds to cell receptors and triggers an intracellular cascade involving ODC and the polyamines, which, in turn, stimulate RNA polymerase, DNA, RNA and protein synthesis, cell division, and adaptive tissue growth.
 ...
PMID:Hormones and polyamines in intestinal and pancreatic adaptation. 392 43

The evidence for an enteropancreatic trophic axis is reviewed. Luminal nutrition is essential for the maintenance of normal intestinal mucosal, as well as exocrine pancreatic structure and function. Exclusion of luminal nutrition leads to mucosal hypoplasia and hypofunction with similar changes in the pancreas. The trophic effect of luminal nutrition may be mediated through the release of regulatory peptides with endocrine or paracrine effects. Enteroglucagon is the strongest candidate for the role of "enterotrophin" while cholecystokinin (CCK) markedly influences pancreatic growth. Thus, CCK not only stimulates exocrine pancreatic secretion but makes acinar cells divide and the pancreas grow. The cellular mechanisms whereby trophic peptides influence normal and adaptive growth are also discussed with emphasis on polyamines (putrescine, spermidine and spermine) and the key enzymes controlling their synthesis (ornithine decarboxylase [ODC]) and degradation (diamine oxidase [DAO]). When polyamine synthesis is blocked with the ODC inhibitor difluoromethyl ornithine (DFMO), the adaptive intestinal hyperplasia of pancreaticobiliary diversion is either inhibited or completely prevented. A proposed sequence of events might be: luminal nutrients, particularly long chain fat, reach the ileum and colon and stimulate increased enteroglucagon release. Enteroglucagon binds to cell receptors and triggers an intracellular cascade involving ODC and the polyamines which, in turn, stimulate RNA polymerase, DNA, RNA and protein synthesis, cell division and adaptive tissue growth.
 ...
PMID:[Potential adaptation of the gastrointestinal system. Existence of an enteropancreatic trophic axis, the role of hormones and polyamines]. 393 Dec 14

1. Fasting causes atrophy of small bowel mucosa which rapidly resolves with luminal feeding. This effect of enteral nutrient may be mediated by stimulation of growth factor secretion. We therefore evaluated whether luminal administration of epidermal growth factor, a peptide hormone found in gastro-intestinal contents and trophic for small bowel mucosa, would prevent the mucosal atrophy associated with starvation. 2. Adult rats were: (i) fasted for 3 days, (ii) fasted and then refed for 1 day or (iii) fasted and then refed for 2 days. During the 2 days before study, animals in each group received infusions of epidermal growth factor (2.5 micrograms/day) or diluent alone into distal jejunum. 3. Epidermal growth factor treatment of fasted animals resulted in a tripling of mucosal ornithine decarboxylase activity (P < 0.001) and a doubling of mucosal DNA content (P < 0.001) in the jejunum, values similar to those of refed animals. Epidermal growth factor infusion in refed rats resulted in a further doubling of mucosal ornithine decarboxylase activity (P < 0.001), but no additional increase in DNA content. Effects of epidermal growth factor infusion were generally greater in jejunum than ileum. 4. In conclusion, luminal exposure to epidermal growth factor prevents starvation-induced mucosal atrophy in the small bowel, but does not enhance the mucosal growth associated with refeeding. Effects are greatest at the site of administration. Luminal epidermal growth factor is a potential mediator of the indirect effects of nutrient on mucosal growth in the small bowel. Enteral administration of epidermal growth factor holds promise for preventing atrophy and maintaining mucosal integrity in starved and post-operative patients.
 ...
PMID:Luminal epidermal growth factor preserves mucosal mass of small bowel in fasting rats. 866 81

Luminal nutrients are the main factors that stimulate ornithine decarboxylase (ODC) activity in rat intestinal mucosa following feeding. The aim of the present study was to determine whether lingual (oral) factors are related to the increase in jejunal ODC activity after feeding. ODC activity in the jejunum and liver was measured 3 hours after refeeding of 48-hour fasted rats. In the first experiment, rats were refed with a regular pellet, powder, or liquid diet. In the second experiment, rats were infused with the liquid diet through a gastric infusion tube following 48 hours' fasting. In the third experiment, the experimental rats had a gastric fistula that allowed free drainage from the stomach of all ingested liquid diet. In the fourth experiment, a truncal vagotomy was performed 1 week before the experiment. The increase of ODC activity in the jejunum of rats fed with the liquid diet was less than that of rats fed with the pellet diet or powder diet. The increase of ODC activity in the jejunal mucosa of rats infused through the gastric tube was less than that of rats fed per os, and the increase of ODC activity in the liver did not differ between these experimental groups. ODC activity did not increase in rats with a gastric fistula. Vagotomy did not affect the increase of jejunal ODC activity after feeding. In conclusion, the increase of ODC activity after feeding was attenuated in rats in which the diet was given by bypassing the mouth. This indicates that lingual factors enhance the increase of ODC activity in the jejunal mucosa after feeding, but the lingual factors alone do not increase ODC activity in the jejunum.
 ...
PMID:Lingual factors enhance the increase of ornithine decarboxylase activity in rat jejunal mucosa after feeding. 884 86

Distribution of ornithine decarboxylase activity in rat intestinal villi and crypts was determined by serially sectioning frozen mucosa and measuring enzyme activity in pools of sections composed of villi or crypts. Contents of the pools was determined by histological examination of representative sections, and simultaneous measurement of sucrase as a marker of villus samples demonstrated excellent separation of villi and crypts. In fasted and ad lib fed rats, enzyme activity was highest in the villus-crypt junctional area and in crypts (P < 0.05). Refeeding after a fast increased enzyme activity 15-fold, with greatest activity in villus tips and the villus-crypt junctional area. Luminal 0.4 M glycine stimulated enzyme activity only in villus and villus-crypt junctional samples, while luminal 10 mM putrescine stimulated activity only in crypts. Parenteral epidermal growth factor caused increased enzyme activity in all mucosal areas, but the 18-28-fold increase in the three villus samples (top, middle and bottom) was significantly greater (P < 0.05) than the 7-9-fold increase in crypt and junctional samples. In rats refed after a fast, parenteral putrescine (2 mmol/kg) depressed enzyme activity in all mucosal areas. Ornithine decarboxylase activity is usually greatest in junctional and crypt cells, and villus and crypt cells respond differently to luminal and systemic stimuli.
 ...
PMID:Distribution and regulation of ornithine decarboxylase activity along the villus-crypt axis in the small intestine. 930 91

This study was performed to determine whether intestinal luminal polyamine concentrations are affected by a high soy protein diet when compared with a high casein diet or a normoprotein casein diet. We also determined the effects of these diets, with differences in polyamines content, on mucosal polyamines and ornithine decarboxylase (ODC) activity to assess cell proliferation. Three groups of eight male Wistar rats were fed either a 50% soy protein diet, a 50% casein diet, or an 18% casein diet as a control. After 4 weeks of feeding, both intestinal content and mucosa were recovered. Polyamines were assayed by high performance liquid chromatography. ODC activity was measured by the release of (14)CO(2) from (14)C-L-ornithine. Luminal putrescine and cadaverine concentrations were higher in the jejunum than in the ileum, suggesting an absorptive process. The highest concentrations of intestinal polyamines were observed in rats fed the soy protein diet (P < 0.05). Only minor differences were observed in mucosal polyamines according to the diets. ODC activity was also higher in the intestinal mucosa of rats fed the high soy protein diet (P < 0.05). These results suggest that intestinal luminal polyamine concentrations and ODC activity are modulated by the dietary protein source.
 ...
PMID:Effects of a high soy protein diet on intestinal polyamines and ornithine decarboxylase activity in rats. 1553 16