title: Role of ornithine decarboxylase and polyamines in camostate (Foy-305)-induced pancreatic growth in rats.
abstract: 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.
authors.affiliation: Department of Medicine, Georg-August University of Göttingen, FRG.
authors.forename: C
authors.initials: C
authors.lastname: Löser
authors.forename: U R
authors.initials: UR
authors.lastname: Fölsch
authors.forename: U
authors.initials: U
authors.lastname: Cleffmann
authors.forename: R
authors.initials: R
authors.lastname: Nustede
authors.forename: W
authors.initials: W
authors.lastname: Creutzfeldt
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000097:blood; D000518:Eflornithine / Q000494:pharmacology; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000378:metabolism*; D010179:Pancreas / Q000032:analysis / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D011073:Polyamines / Q000032:analysis*; D011700:Putrescine / Q000032:analysis / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013095:Spermidine / Q000032:analysis / Q000502:physiology; D013096:Spermine / Q000032:analysis / Q000502:physiology
chemical_list: D004952:Esters; D006146:Guanidines; D011073:Polyamines; C034532:camostat; D013096:Spermine; D016670:Gabexate; D002766:Cholecystokinin; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine