A role for B1 and B2 kinin receptors in the modulation of T-kininogen during the acute phase response of inflammation.
Kinin antagonists at B1 and B2 receptors were examined on liver and serum concentrations of immunoreactive T-kininogen and its gene expression in a rat model of carrageenan-induced hindpaw edema. Whereas the B2 antagonist, HOE140, dose-dependently inhibited the paw edema induced by intraplantar injection of carrageenan, the B1 receptor agonist [Sar(D-Phe8)des-Arg9]BK and antagonist [Lys(Leu8)des-Arg9]BK were ineffective. On its own, HOE140 (3.25 x 10(-7) mol/ paw, intraplantar) had no effect on liver and serum T-kininogen levels but it significantly enhanced liver T-kininogen concentrations in rats pretreated with carrageenan at 8 and 24 h postinjection. In the liver, the most pronounced effect was seen at 24 h (treated 248 +/- 7 micrograms/g vs. untreated 113 +/- 9 micrograms/g). The same dose of HOE140 increased serum T-kininogen from 1255 +/- 57 to 1696 +/- 83 micrograms/ml at 24 h. HOE140 did not affect tissue albumin content during the same period. Transcript measurements revealed that the steady-state level of liver T2-kininogen mRNA was specifically increased by HOE140 during inflammation. In carrageenan-treated rats, the B1 antagonist [Lys(Leu8)des-Arg9]BK also significantly increased liver T-kininogen at 24 h. The present results support a role for B2 kinin receptors in the early phase of acute phase protein synthesis and of both B2 and B1 receptors in the late phase (24 h). Hence, systemic effects of kinins should be taken into account in the pharmacology and physiopathology of B1 and B2 kinin receptors in inflammation.
Raymond
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P
Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Décarie
A
A
Lantin
F
F
Raut
R
R
Morais
R
R
Couture
R
R
Adam
A
A
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D007249:Inflammation / Q000378:metabolism*; D007704:Kininogens / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D007704:Kininogens; D018002:Receptors, Bradykinin; C065679:icatibant; D001920:Bradykinin