The influence of nitric oxide on basal and cholecystokinin-8-induced proliferation and apoptosis in the rat pancreas.
Nitric oxide (NO) is formed by different cell types in the pancreas. In this study, inhibition of endogenous nitric oxide by N(omega)-nitro-L-arginine (L-NNA) reduced the urinary excretion of NO(2)/NO(3) and raised serum L-arginine and the NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion of NO(2)/NO(3). The peptide cholecystokinin-8 (CCK-8) has a strong influence on exocrine pancreatic proliferation. Rat pancreas was excised and studied with regard to tissue weight, protein and DNA contents after 3 days of treatment with saline, L-NNA or SNAP given separately or combined with CCK-8. Further, proliferation of different pancreatic cells was studied with [3H]-thymidine incorporation and apoptotic activity was studied by analysing caspase-3 activity and histone-associated DNA fragments. The effects of L-NNA indicate that endogenous nitric oxide formation has a tonic inhibition on apoptosis in the pancreas during both basal condition and growth stimulation by CCK-8. In CCK-induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates ductal cells. Endogenous NO may regulate the balance between proliferation and apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell turnover in the pancreas.
Trulsson
Lena M
LM
Department of Biomedicine and Surgery, Faculty of Health Sciences, University Hospital, SE-581 85 Linköping, Sweden.
Gasslander
Thomas
T
Sundqvist
Tommy
T
Svanvik
Joar
J
D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000097:blood; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D002956:Citrulline / Q000097:blood; D004247:DNA / Q000032:analysis; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D019335:Nitroarginine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
D010446:Peptide Fragments; C410885:cholecystokinin 8; D019335:Nitroarginine; D002956:Citrulline; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D004247:DNA; D002766:Cholecystokinin; D001120:Arginine; D000681:Amylases; D020169:Caspases