Blockade of bradykinin B(2) receptor suppresses acute pancreatitis induced by obstruction of the pancreaticobiliary duct in rats.
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.
Hirata
Mitsuhiro
M
Department of Surgery, Kitasato University School of Medicine, Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Hayashi
Izumi
I
Yoshimura
Kuniko
K
Ishii
Ken-ichiro
K
Soma
Kazui
K
Ohwada
Takashi
T
Kakita
Akira
A
Majima
Masataka
M
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001652:Bile Ducts / Q000473:pathology / Q000601:surgery; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000503:physiopathology; D007704:Kininogens / Q000378:metabolism; D008049:Lipase / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D010183:Pancreatic Ducts / Q000473:pathology / Q000601:surgery; D010195:Pancreatitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D010446:Peptide Fragments / Q000097:blood; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D014867:Water / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; C105311:FR 173657; D007704:Kininogens; D010446:Peptide Fragments; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D014867:Water; C079000:bradykinin (1-5); C065679:icatibant; D008049:Lipase; D000681:Amylases; D001920:Bradykinin