Role of ornithine decarboxylase and polyamines in camostate (Foy-305)-induced pancreatic growth in rats.
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.
Löser
C
C
Department of Medicine, Georg-August University of Göttingen, FRG.
Fölsch
U R
UR
Cleffmann
U
U
Nustede
R
R
Creutzfeldt
W
W
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
D004952:Esters; D006146:Guanidines; D011073:Polyamines; C034532:camostat; D013096:Spermine; D016670:Gabexate; D002766:Cholecystokinin; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine