Back to Search
Start Over
Blockade of bradykinin B(2) receptor suppresses acute pancreatitis induced by obstruction of the pancreaticobiliary duct in rats.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2002 Jan; Vol. 135 (1), pp. 29-36. - Publication Year :
- 2002
-
Abstract
- 1. The involvement of bradykinin (BK) B(2) receptor in acute pancreatitis induced by pancreaticobiliary duct ligation was investigated in rats. 2. The activities of amylase and lipase in the serum, the water content of the pancreas, and vacuolization of the acinar cells were significantly increased 2 h after obstruction of the duct in Sprague-Dawley rats. 3. Elevated serum amylase activity, increased pancreatic oedema, and damage of the pancreatic tissue were significantly less marked in plasma kininogen-deficient, B/N-Katholiek rats than in the normal strain, B/N-Kitasato rats 2 h after the ligation. 4. Obstruction of the pancreaticobiliary duct augmented the level of (1-5)-BK (Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)), a stable BK metabolite, in the blood from 73.0+/-21.7 pg ml(-1) at 0 h to 149.8+/-38.0 pg ml(-1) at 2 h after the induction of pancreatitis in SD rats. 5. Administration of a BK B(2) receptor antagonist, FR173657 (100 mg kg(-1), p.o.) or Hoe140 (100 nmol kg(-1), s.c.), reduced the elevation of amylase and lipase activities in the serum and of pancreatic water content in a dose-dependent manner. The effective attenuation of oedema formation and vacuolization by the antagonists was also confirmed light-microscopically. In contrast, treatment with gabexate mesilate or indomethacin did not cause significant suppression of the pancreatitis. 6. These findings suggest a possible involvement of kinin B(2) receptor in the present pancreatitis model. Furthermore, they point to the potential usefulness of the B(2) receptor in clinical acute pancreatitis.
- Subjects :
- Acute Disease
Amylases blood
Amylases drug effects
Amylases metabolism
Animals
Bile Ducts pathology
Bile Ducts surgery
Bradykinin blood
Dose-Response Relationship, Drug
Edema physiopathology
Kininogens metabolism
Lipase blood
Lipase drug effects
Lipase metabolism
Male
Pancreas enzymology
Pancreas pathology
Pancreatic Ducts pathology
Pancreatic Ducts surgery
Pancreatitis etiology
Pancreatitis pathology
Peptide Fragments blood
Rats
Rats, Inbred Strains
Rats, Sprague-Dawley
Receptor, Bradykinin B2
Water metabolism
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Bradykinin analogs & derivatives
Bradykinin pharmacology
Bradykinin Receptor Antagonists
Pancreatitis physiopathology
Quinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 135
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11786477
- Full Text :
- https://doi.org/10.1038/sj.bjp.0704462