摘要:

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. α-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 2 h; 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). α-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 r

ISSN:0012-2823    

DOI:10.1159/000199867

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Oxygen-derived free radicals are cytotoxic and mediate tissue damage. Allopurinol prevents the formation of superoxide radicals and dimethyl sulphoxide (DMSO) scavenges the hydroxyl ones. Intraperitoneal reserpine (5 mg/kg every day for 5 days) produced chronic gastric ulceration in all rats after 4 weeks. Animals gavaged with 1 ml/day of each of 1 % allopurinol and 1 % DMSO for 4 weeks developed ulceration in 60 % of cases; however this ulceration developed in only 20% of animals similarly gavaged with 2% solutions. Rats gavaged with 1 ml/day of each of 5 % allopurinol and 5 % DMSO for 4 weeks were completely protected against the reserpine-induced chronic gastric ulceration. This protection was not associated with any significant effect on the H+ output of the rat stomach. The results suggest that in the rat, oxygen-derived free radicals are responsible for the development of chronic gastric ulceration and that removing these radicals protects against the said ulceration without influencing acid secretion, i.e. cytoprotection.

ISSN:0012-2823    

DOI:10.1159/000199868

出版商:S. Karger AG    

年代:1989

数据来源: Karger