Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Griesbacher, T; Rainer, I; Tiran, B; Fink, E; Lembeck, F; Peskar, BA.
Mechanism of kinin release during experimental acute pancreatitis in rats: evidence for pro- as well as anti-inflammatory roles of oedema formation.
Br J Pharmacol. 2003; 139(2):299-308
Doi: 10.1038/sj.bjp.0705247
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- Führende Autor*innen der Med Uni Graz
- Griesbacher Thomas
- Co-Autor*innen der Med Uni Graz
- Lembeck Fred
- Peskar Bernhard
- Tiran Beate
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- Abstract:
- 1 Kinin B(2) receptor antagonists or tissue kallikrein (t-KK) inhibitors prevent oedema formation and associated sequelae in caerulein-induced pancreatitis in the rat. We have now further investigated the mechanism of kinin generation in the pancreas. 2 Kinins were elevated in the pancreatic tissue already before oedema formation became manifest. Peak values (421+/-59 pmol g(-1) dry wt) were reached at 45 min and remained elevated for at least 2 h; a second increase was observed at 24 h. Pretreatment with the B(2) receptor antagonist icatibant abolished kinin formation, while post-treatment was ineffective. 3 Total kininogen levels were very low in the pancreas of controls, but increased 75-fold during acute pancreatitis. This increase was absent in rats that were pretreated with icatibant. 4 During pancreatitis, t-KK-like and plasma kallikrein (p-KK)-like activity in the pancreas, as well as trypsinogen activation peptide (TAP) increased significantly. Icatibant pretreatment further augmented t-KK about 100-fold, while p-KK was significantly attenuated; TAP levels remained unaffected. 5 Endogenous protease inhibitors (alpha(1)-antitrypsin, alpha(2)-macroglobulin) were low in normal tissues, but increased 45- and four-fold, respectively, during pancreatitis. This increase was abolished when oedema formation was prevented by icatibant. 6 In summary, oedema formation is initiated by t-KK; the ensuing plasma protein extravasation supplies further kininogen and active p-KK to the tissue. Concomitantly, endogenous protease inhibitors in the oedema fluid inhibit up to 99% of active t-KK. Our data thus suggest a complex interaction between kinin action and kinin generation involving positive and negative feedback actions of the inflammatory oedema.
- Find related publications in this database (using NLM MeSH Indexing)
- Acute Disease -
- Animals -
- Anti-Inflammatory Agents, Non-Steroidal - pharmacology
- Bradykinin - analogs and derivatives
- Caerulein - analogs and derivatives
- Edema - metabolism
- Enzyme Activation - metabolism
- Female - metabolism
- Kininogens - metabolism
- Kinins - antagonists and inhibitors
- Pancreas - metabolism
- Pancreatitis - chemically induced
- Plasma Kallikrein - metabolism
- Rats - metabolism
- Rats, Sprague-Dawley - metabolism
- Receptors, Cell Surface - antagonists and inhibitors
- Serine Proteinase Inhibitors - metabolism
- Tissue Kallikreins - metabolism
- Trypsinogen - metabolism
- alpha 1-Antitrypsin - metabolism
- alpha-Macroglobulins - metabolism
- Find related publications in this database (Keywords)
- kallikrein-kinin system
- pancreatitis
- inflammation
- kinins
- bradykinin
- kininogen
- kallikrein
- alpha(1)-antitrypsin
- alpha(2)-macroglobulin