Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The trophic effect of one or multiple subcutaneous injections of two different doses of a cholecystokinin-like peptide (CCK-LP) on the rat pancreas was evaluated by determination of ornithine decarboxylase (ODC) activity, the concentrations of the polyamines putrescine, spermidine, and spermine, and the activities of DNA polymerase and thymidine kinase, in addition to the contents of DNA, RNA, and protein. ODC activity was increased 10- to 20-fold already 2 h after a single injection of CCK-LP. The activity thereafter decreased and approached the control level after 6 to 8 h. The concentration of putrescine also showed a marked increase after a single injection, approaching maximum at 8 h. A slight increase was found for spermidine as well. DNA polymerase and thymidine kinase increased after 2 days of treatment. The DNA content was still normal at that time. The study suggests that the trophic effect of CCK is initiated very early. It shows that ODC activity and putrescine concentrations are early and sensitive determinants of the effect of CCK on the pancreas.
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PMID:Effects of a cholecystokinin-like peptide on DNA and polyamine synthesis in the rat pancreas. 241 Sep 73

Little is known about the cellular mechanisms responsible for the trophic effects of cholecystokinin (CCK) and secretin on the rat pancreas, and controversy exists with regard to the interaction between these two peptides. In the present study attempts were made to elucidate the time course of events leading to pancreatic growth and to clarify the interaction between the peptides when given as continuous, long-term intravenous infusions to rats. A cholecystokinin-like peptide (CCK-LP) and secretin were given as a continuous intravenous infusion to conscious and unrestrained animals with free access to food and water for 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 96 h. The pancreas was quickly removed and analyzed for variables indicating synthesis and accumulation of DNA, RNA, and polyamines. CCK-LP increased the activity of RNA polymerase already after 1 h, whereas an increase in the activity of ornithine decarboxylase (ODC) and the level of putrescine was seen at 4 h. Spermidine was increased after 12 h. The activities of DNA polymerase and thymidine kinase were increased at 12 and 24 h, respectively, whereas the total contents of DNA and RNA were first increased at 48 h. Secretin alone showed a marked but short-lived effect on polyamine synthesis and a weak effect on the variables indicating protein synthesis and growth. When the two peptides were given together, a large but transient potentiation of ODC activity was observed, whereas no interaction was seen on polyamines, RNA synthesis, or pancreatic growth. The present study confirms the trophic effects of CCK and secretin on the rat pancreas but fails to confirm an interaction between the two peptides on growth. Both peptides stimulate polyamine synthesis, and ODC appears to be an early and sensitive indication of their trophic effect. The initiation of RNA synthesis appears to be independent of the ODC activity.
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PMID:Short- and long-term effects of secretin and a cholecystokinin-like peptide on pancreatic growth and synthesis of RNA and polyamines. 247 84

The role played by the polyamines in mediating the pancreatic growth and secretory responses to hormonal stimulation is uncertain. The effect of an inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethylornithine (DFMO), on rat pancreatic protein secretion and synthesis and on growth in response to hormonal stimulation was therefore studied. Anesthetized rats were given an intravenous injection of DFMO (50, 100, or 150 mg/kg), followed by a 7-h continuous infusion (15, 25, or 35 mg/kg/h, respectively). After a basal 1-h period an intravenous infusion of 2.5 micrograms/kg/h of the cholecystokinin-like peptide Thr28Nle31CCK25-33 (CCK-LP) was added and continued for 6 h. The control rats received CCK-LP only. The ODC activity in the pancreas was markedly reduced by DFMO, but DFMO did not affect pancreatic juice volume or protein output. In another series conscious rats were given a continuous intravenous infusion of 2.5 micrograms/kg/h of CCK-LP for 8, 24, and 48 h or 5.0 micrograms/kg/h of secretin for 8 and 48 h, with or without DFMO (100 mg/kg as an injection initially and thereafter 25 mg/kg/h). The ODC activity and putrescine concentration in the pancreas were significantly reduced by DFMO at 8 and 24 h but not at 48 h. DFMO also significantly reduced the activities of RNA polymerase, DNA polymerase, and thymidine kinase at 24 h, but not at 48 h. The present study thus indicates that polyamines play a role in the initiation of the growth response to hormonal stimulation but does not support a similar dependence for early pancreatic protein synthetic and secretory responses.
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PMID:Inhibition of polyamine synthesis by alpha-difluoromethylornithine and its effects on pancreatic secretion and growth in the rat. 247 85

Acute and long-term changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to cholecystokinin administration (1 microgram kg-1 body wt every 8 h) were studied in rats. alpha-difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. In the cholecystokinin-treated animals ornithine decarboxylase activity was increased after 2 h, reached a maximum after 8 h (444.6 pmol 14CO2 h-1 mg-1 DNA, about 65-fold greater than controls, P less than 0.001) followed by a significant increase of putrescine after 6 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (24 h), pancreatic weight (2 days), protein (2 days) and DNA (5 days). alpha-difluoromethylornithine significantly delayed the increase in ornithine decarboxylase, putrescine and spermidine as well as all trophic parameters. Increases in ornithine decarboxylase, polyamines and all trophic parameters were completely inhibited by simultaneous application of the CCK receptor antagonist L-364,718. These data indicate an important role for ornithine decarboxylase and polyamines in cholecystokinin-induced pancreatic growth in rats.
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PMID:Ornithine decarboxylase and polyamines in cholecystokinin-induced pancreatic growth in rats: effects of alpha-difluoromethylornithine and the CCK receptor antagonist L-364,718. 247 58

The dose dependence of a cholecystokinin-like peptide (CCK-LP) on the trophic response in the rat pancreas was studied. Graded doses of Thr28Nle31CCK25-33 (0.02, 0.1, 0.5, 2.5, and 12.5 micrograms/kg/h) or saline were given as a continuous intravenous infusion to conscious and fed rats for 8 and 48 h. Secretin (5.0 micrograms/h) was given alone or combined with the three highest doses of CCK-LP for 48 h. CCK-LP showed a dose-dependent stimulating effect on pancreatic growth and synthesis of RNA and polyamines. The threshold dose ranged from 0.02 to 0.5 micrograms/kg/h and was lowest for stimulation of ornithine decarboxylase (ODC). The maximal effects on protein, RNA, and DNA contents were achieved with 2.5 micrograms/kg/h. These same variables markedly decreased with 12.5 micrograms/kg/h, whereas marked further increases were found for the activities of RNA polymerase, DNA polymerase, and thymidine kinase. This same dose of CCK-LP caused after 8 h of treatment a marked and transient increase in pancreatic weight, activity of ODC, and concentration of putrescine. When secretin was added to 0.5 and 2.5 micrograms/kg/h of CCK-LP, no additional effect (except for ODC) was found. When secretin was added to the highest dose of CCK-LP, the decreased contents of protein and RNA were significantly increased, and the markedly increased activities of RNA- and DNA-synthesizing enzymes were significantly decreased. The present study shows a clear dose-response relationship for the trophic effect of CCK-LP on the rat pancreas and indicates that the growth effect of a supramaximal dose includes components of regeneration secondary to damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of graded doses of a cholecystokinin-like peptide with and without secretin on pancreatic growth and synthesis of RNA and polyamines in rats. 248 Jun 34

This study was designed to investigate changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to feeding of the synthetic protease inhibitor camostate. alpha-Difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Cholecystokinin (CCK) plasma levels in camostate-fed rats increased from basal values of 3-4 pmol/l to a maximal level of 27.4 pmol/l after 2h; they then decreased up to 12 h but remained elevated above controls throughout the 30-day experiments. In the camostate group pancreatic ornithine decarboxylase activity was elevated after 2 h, reaching a maximum after 6 h (1,858.5 pmol 14CO2/h/mg DNA, about 200-fold above controls) followed by a significant increase in putrescine after 4 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (12 h), protein (24 h), pancreatic weight (24 h) and DNA (5 days). alpha-Difluoromethylornithine significantly delayed and reduced the camostate-induced increase in ornithine decarboxylase activity and polyamine concentrations as well as the trophic parameters. Application of the CCK receptor antagonist L-364,718 resulted in complete inhibition of the increases in ornithine decarboxylase, polyamines and all trophic parameters. These data indicate an important role for ornithine decarboxylase and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation in rats.
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PMID:Role of ornithine decarboxylase and polyamines in camostate (Foy-305)-induced pancreatic growth in rats. 250 68

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