Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Griesbacher, T; Rainer, I; Tiran, B; Evans, DM.
Involvement of tissue kallikrein but not plasma kallikrein in the development of symptoms mediated by endogenous kinins in acute pancreatitis in rats.
Br J Pharmacol. 2002; 137(5):692-700
Doi: 10.1038/sj.bjp.0704910
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Griesbacher Thomas
- Co-Autor*innen der Med Uni Graz
- Tiran Beate
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- In order to investigate the mechanism of kinin release leading to vascular symptoms in acute interstitial-oedematous pancreatitis, the novel, selective inhibitors of tissue kallikrein, (2S,2'R)-2-(2'-amino-3'-(4'-chlorophenyl)propanoylamino)-N-(3-guanidinopropyl)-3-(1-naphthyl)propanoamide (FE999024, CH-2856), and of plasma kallikrein, (2'S,2"R)-4-(2'-(2"(carboxymethylamino)-3"-cyclohexyl-propanoylamino)-3'-phenyl-propanoylamino)piperidine-1-carboxamidin (FE999026, CH-4215), were used in experimental caerulein-induced pancreatitis in rats. Oedema formation and plasma protein extravasation during the 2 h infusion of caerulein were inhibited in a dose-dependent manner by i.p. pretreatment with FE999024 (7-60 micromol kg(-1)) while FE999026 had no effect at the same doses. Haemoconcentration and hypovolaemia associated with the pancreatic oedema formation during pancreatitis were significantly attenuated by FE999024 at a dose of 20 micro mol kg(-1). The reduction in circulating plasma volume was not affected by FE999026. Accumulation of amylase and lipase in the pancreas was dose-dependently reduced by FE999024 while enzyme activities in the blood serum were increased by FE999024 at 60 micromol kg(-1) indicating improved enzyme removal from the tissue. Enzyme activities in the tissue and in the blood remained unaffected by FE999026. FE999024 (20 micromol kg(-1)) largely inhibited increased tissue kallikrein-like activity in the pancreas during acute pancreatitis and also strongly attenuated influx of plasma kallikrein into the tissue. FE999026 (20 micromol kg(-1)) significantly inhibited plasma kallikrein-like activity in the pancreas but had no effect on tissue kallikrein-like activity. In conclusion, vascular kinin-mediated symptoms observed during oedematous pancreatitis in the rat are caused by the action of tissue kallikrein in the pancreas whereas an involvement of plasma kallikrein seems to be unlikely.
- Find related publications in this database (using NLM MeSH Indexing)
- Acute Disease -
- Animals -
- Dose-Response Relationship, Drug -
- Female -
- Kinins - metabolism
- Pancreatitis - chemically induced
- Peptides - chemistry
- Plasma Kallikrein - antagonists and inhibitors
- Rats - antagonists and inhibitors
- Rats, Sprague-Dawley - antagonists and inhibitors
- Tissue Kallikreins - antagonists and inhibitors
- Find related publications in this database (Keywords)
- kallikrein inhibitors
- FE999024
- FE999026
- tissue kallikrein
- plasma kallikrein
- pancreatitis
- inflammation