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)

We examined the role of physiologic plasma concentrations of cholecystokinin (CCK) in the regulation of rat pancreatic gene expression. Postprandial plasma CCK concentrations, as determined by bioassay, were achieved by intraduodenal perfusion with soybean trypsin inhibitor (SBTI) or intravenous infusion of CCK-8. SBTI administration for 48h resulted in nonparallel regulation of digestive enzyme gene expression, as assessed by slot-blot analysis using cloned cDNA probes for trypsin, chymotrypsin, amylase and ribonuclease. As an indicator for pancretic growth stimulation, ornithine decarboxylase (ODC) gene expression was stimulated appr. 2-fold over the SBTI infusion period. Identical effects were seen with i.v. infusion of CCK-8. The CCK receptor antagonist L-364, 718 blocked the effects on pancreatic gene expression of both CCK infusion and SBTI administration. These data therefore indicate that postprandial plasma CCK concentrations regulate pancreatic digestive enzyme and ODC gene expression at a pretranslational level.
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PMID:Cholecystokinin as a regulator of rat pancreatic gene expression. 171 83

The present study was designed to investigate the effects of acute and chronic application of the immunosuppressive agent cyclosporine A (CsA) on pancreatic polyamine metabolism as well as pancreatic growth of rats in vivo. Seven to ten animals per group were treated with either the synthetic trypsin inhibitor camostate (FOY-305, 200 mg/kg b.wt. p.o. twice a day), CsA (10 mg/kg b.wt. p.o. once a day), camostate plus CsA, or oil as control, and animals were killed after 8 h, 1, 5 and 14 days. Feeding of camostate resulted in a significant increase of the measured parameters in the following time-course: cholecystokinin (CCK), 8 h; ornithine decarboxylase (ODC), 8 h: putrescine, 8 h; S-adenosylmethionine decarboxylase (SAM-DC), 1 day; pancreatic weight, 1 day; protein content, 5 days; spermidine, 5 days; RNA, 5 days; and DNA, 14 days. Simultaneous treatment with CsA resulted in a significant inhibition of camostate-induced increases in ODC, SAM-DC as well as putrescine and spermidine and furthermore caused a nearly complete inhibition of the increase of all trophic parameters, while CCK plasma levels were not altered. Counterregulatory mechanisms to maintain the intracellular polyamine pool as known after application of specific inhibitors of enzymes of the polyamine metabolism (i.e. DFMO) were not observed. Therefore we conclude that CsA does not directly interact with the polyamine metabolism, but rather with the second messenger system or any other intracellular mechanism, that is activated after stimulation with CCK before the polyamine metabolism is induced.
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PMID:Acute and chronic effects of cyclosporine A on pancreatic polyamine metabolism and pancreatic adaptation. 226 69

Ornithine decarboxylase (ODC) was induced in rat small intestine by treatment with hypotonic solution in vitro and purified by two procedures, a conventional procedure and an immunoaffinity procedure. SDS-polyacrylamide gel electrophoresis showed that the molecular weight of the preparation purified by the immunoaffinity procedure (Mr = 53,000) was slightly larger than that of the preparation obtained by the conventional procedure (Mr = 52,000). Values for the Km for L-ornithine (0.1 mM), the isoelectric point (5.4), and the final specific activity (5.1-5.5 x 10(5) nmol CO2/mg protein/30 min) of the two preparations were similar to those reported for the rat liver ODC. Addition of a protease inhibitor (limabean trypsin inhibitor) to the crude extract prevented the appearance of the smaller enzyme (Mr = 52,000) obtained by the conventional purification procedure. Our result indicates that the large enzyme is native ODC and the smaller one is a partial proteolysis product of native ODC.
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PMID:Purification and some properties of rat intestinal ornithine decarboxylase. 250 67

The effect of cyclosporine A (CsA) and alpha-difluoromethylornithine (DFMO) on the camostate-induced increase in pancreatic ornithine decarboxylase (ODC) activity and polyamine biosynthesis has been studied in vivo. Six hours after application of the synthetic trypsin inhibitor camostate (200 mg/kg b wt orally) pancreatic ODC activity increased about 140-fold and putrescine concentration about ninefold. CsA inhibited the elevation of both parameters in a dose-dependent manner. CsA pretreatment for 3 d with doses of 7.5, 10.0, and 12.5 mg/kg b wt orally once a day and consecutive CsA blood levels 24 h after the last CsA application of 751 +/- 62, 968 +/- 70, and 1,395 +/- 79 ng/mL, respectively, resulted in a complete inhibition of the camostate-stimulated increase in pancreatic ODC activity and putrescine concentration in vivo. DFMO (2% in drinking water and additionally 300 mg/kg b wt intraperitoneally at 8 AM, 12 noon, and 4 PM) inhibited the increase in both, ODC activity, and putrescine, significantly in an equipotent degree as 2.5 mg CsA/kg b wt, whereas higher doses of CsA proved to be more effective than DFMO in the chosen subtoxic dose. In all cases, no significant changes in pancreatic spermidine and spermine concentration, DNA and protein content, or pancreatic and body weight were observed. It is concluded that CsA in doses used for immunosuppression in clinical practice is a very potent and more effective inhibitor of ODC activity and polyamine synthesis in vivo than DFMO. This ODC inhibitory effect of CsA is a further detail to elucidate the up to now incompletely understood mechanisms of action of this immunosuppressive agent.
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PMID:Dose-dependent inhibition by cyclosporine A of the induction of pancreatic ornithine decarboxylase (ODC) in rats. 260 Apr 52

The effects of cholecystokinin (CCK) on pancreatic ornithine decarboxylase (ODC) gene expression were studied in the rat. Plasma CCK concentrations were raised to levels comparable to postprandial values either by intravenous infusion of CCK octapeptide (CCK-8) or by intraduodenal perfusion of soybean trypsin inhibitor (SBTI). ODC mRNA levels were quantified using a cloned cDNA probe. ODC mRNA increased to 166 +/- 34% (n = 4) of control after 1 h, peaked at 254 +/- 39% (n = 4) of control after 24 h, and remained significantly elevated for up to 48 h of SBTI infusion. Intravenous infusion of CCK-8 for 24 h increased ODC mRNA levels to the same extent observed with SBTI infusion. The CCK receptor antagonist L364,718 by itself had no effect on ODC mRNA levels but totally abolished the induction of ODC mRNA by both intravenous CCK infusion and intraduodenal infusion of SBTI. These data therefore indicate that CCK plasma concentrations comparable to postprandial values regulate pancreatic ODC at a pretranslational level and that SBTI exerts its effects on pancreatic ODC via an increase in plasma CCK.
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PMID:Effects of cholecystokinin on pancreatic ornithine decarboxylase gene expression. 320 75

This study was designed to investigate the role of ornithine decarboxylase (ODC) and polyamines in pancreatic adaptation. Cholecystokinin (CCK) is well-known to be a potent trophic stimulus on the pancreas. On the other hand, the oral application of the synthetic trypsin inhibitor camostate results in an extensive release of endogenous CCK in rats. alpha-difluoromethylornithine (DFMO), an irreversible and specific inhibitor of ODC, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Camostate feeding (200 mg/kg b.wt. orally twice a day) resulted in a rapid elevation of ODC activity already after 2 hours, reaching a maximum after 6 hours (about 200fold above controls) followed by a significant increase in putrescine after 4 hours and spermidine after 24 hours while spermine remained unchanged. The trophic parameters increased as expected in following time-course: thymidine kinase (12 hours), DNA polymerase (12 hours), protein (24 hours), pancreatic weight (24 hours) and DNA (5 days). DFMO (2% in drinking water + 3 x 300 mg/kg b.wt. i.p. during daytime) was not able to prevent but significantly delayed and reduced the camostate-induced increase in ODC and polyamines as well as the trophic parameters. These data indicate an essential role for ODC and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation.
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PMID:Ornithine decarboxylase and polyamine biosynthesis in pancreatic adaptation. 325 34

The induction of ornithine decarboxylase activity in weanling rat pancreas by a trypsin inhibitor-containing soy protein isolate has been studied. Oral administration of the isolate at 0.8, 1.6, 4.0, 6.0, and 8.0 mg/g body wt produced marked elevations in enzyme activity, a response which was proportional to the amount of isolate administered. Ornithine decarboxylase activity was measured at 2, 4, 6, 8, 12, and 24 hr after the isolate was given. A statistically significant increase in enzyme activity was evident as early as 2 hr after treatment; maximal activity occurred at 6 hr and was approximately 140 times greater than the
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PMID:Induction of ornithine decarboxylase activity in weanling rat pancreas by an orally administered soy protein isolate. 356 21

Aim of the present study was to evaluate the role of cellular uptake of dietary [3H]putrescine for the regulation of pancreatic, hepatic, and small intestinal polyamine metabolism during normal and camostate-induced pancreatic growth in rats in vivo. Initially dose-response and time-course studies of [3H]putrescine uptake were performed. Male Wistar rats were either treated with the synthetic trypsin inhibitor camostate (200 mg/kg body wt orally twice daily), camostate plus the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) (2% in drinking water plus 3 x 300 mg/kg body wt intraperitoneally during daytime) or saline as controls. After 4, 8, 12, 24, 36, 48, or 120 hr, five to seven animals per group were killed, respectively. Orally fed [3H]putrescine (10 nmol/kg body wt. 2 hr prior to death) is rapidly taken up and further metabolized to spermidine in normal growing pancreas, liver, and small intestine. Feeding of camostate significantly enhanced dietary [3H]putrescine uptake, while simultaneous inhibition of de novo synthesis of intracellular polyamines by DFMO resulted in a highly significant further increase in cellular uptake of orally fed [3H]putrescine, which is immediately metabolized to spermidine. The present in vivo data confirm the important role of dietary putrescine uptake for the maintenance of intracellular polyamine pool in normal and stimulated pancreatic growth. Furthermore, dietary putrescine uptake is an important regulatory mechanism to maintain the normal and growth-stimulated cellular polyamine pool in the pancreas after potent simultaneous inhibition of intracellular de novo polyamine synthesis.
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PMID:Uptake of extracellular, dietary putrescine is an important regulatory mechanism of intracellular polyamine metabolism during camostate-induced pancreatic growth in rats. 907 31

The present study was designed to investigate the inhibitory potency of the two novel S-adenosylmethionine decarboxylase (SAM-DC) inhibitors MDL 73811 and CGP 48664 on the camostate-induced pancreatic polyamine metabolism and especially intracellular spermidine accumulation as well as pancreatic growth in vivo. Male Wistar rats (180 g) were either treated with (1) the synthetic trypsin inhibitor camostate (200 mg/kg b.w. orally twice daily), (2) camostate+MDL 73811 (100 mg/kg b.w. i.p. twice daily), (3) camostate+CGP 48664 (5 mg/kg b.w. i.p. once daily) or (4) saline as controls. Animals (5-9 per group) were sacrificed after 1, 2 and 5 days of treatment. MDL 73811 caused a long-lasting (> 95%; p < 0.005) inhibition of SAM-DC followed by a significant (p < 0.005) increase in ornithine decarboxylase and putrescine, while spermine was decreased (p < 0.005). In contrast to MDL 73811, CGP 48664 had little effect in vivo. Despite potent inhibition of SAM-DC camostate-stimulated intracellular spermidine accumulation was not prevented by the simultaneous administration of MDL 73811. Consequently organ growth was not affected either. Since de novo synthesis of spermidine was effectively inhibited by MDL 73811, counterregulatory mechanisms (i.e. interconversion pathway, extracellular uptake) had to step in to maintain the intracellular balance of spermidine. The present data support the general concept of the importance of intracellular spermidine accumulation for the maintenance of pancreatic growth in vivo.
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PMID:Importance of intracellular S-adenosylmethionine decarboxylase activity for the regulation of camostate-induced pancreatic polyamine metabolism and growth: in vivo effect of two novel S-adenosylmethionine decarboxylase inhibitors. 924 21