Acute and chronic effects of cyclosporine A on pancreatic polyamine metabolism and pancreatic adaptation.
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.
Löser
C
C
Department of Medicine, Georg-August-University of Göttingen, FRG.
Alves
F
F
Stöckmann
F
F
Fölsch
U R
UR
Creutzfeldt
W
W
D000123:Acetyltransferases / Q000378:metabolism; D000222:Adaptation, Physiological / Q000187:drug effects; D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D002766:Cholecystokinin / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology*; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014361:Trypsin Inhibitors / Q000494:pharmacology; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D012437:Adenosylmethionine Decarboxylase; D015317:Biogenic Polyamines; D002766:Cholecystokinin; D003524:Cyclosporins; D004952:Esters; D016670:Gabexate; D006146:Guanidines; D009955:Ornithine Decarboxylase; D014361:Trypsin Inhibitors; D000099228:Diamine N-Acetyltransferase; C034532:camostat