Analysis of the mechanisms involved in the inflammatory response induced by des-Arg9-bradykinin in the rat pleural cavity.
OBJECTIVE
The present study investigates some of the mechanisms underlying the inflammatory responses caused by the selective B1 kinin receptor agonist, des-Arg9-bradykinin (des-Arg9-BK), in the rat pleural cavity.


METHODS
Male Wistar rats were used (N = 4-10 per group).


METHODS
A fixed volume (100 microl) of PBS or des-Arg9-BK (10-60 nmol) was injected into the rat pleural cavity. Animals were treated with the B1 des-Arg9[Leu8]-BK (60 nmol/cav.) and R715 (65 nmol/cav.), B2 HOE 140 (3 nmol/cav.), NK1 FK888 (1 nmol/cav.), NK2 SR 48968 (20 nmol/cav) or NK3 SR142801 (10 nmol/cav.) receptor antagonists, or with either cyproheptadine (40 mg/kg, i.p.) or compound 48/80 (0.6 mg/kg, i.p., twice a day/3 days, 1.2 mg/kg/4th day).


RESULTS
des-Arg9-BK (30 nmol/cavity) induced a time-dependent leukocyte migration. The increase in total leukocytes was not significantly reduced by the treatment with any of the B1, B2, NK1, NK2 or NK3 receptor antagonists. Treatment of animals with cyproheptadine or with compound 48/80 markedly inhibited des-Arg9-BK-induced cell migration (77 +/- 7 and 82 +/- 4%, respectively).


CONCLUSIONS
These findings suggest that inflammatory responses caused by the B1 agonist des-Arg9-BK in the rat pleural cavity are mediated by a receptor-independent mechanism, being largely dependent on the activation of resident mast cells and release of histamine and/or serotonin.
Pinheiro
R M
RM
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianopólis, Brazil.
Campos
M M
MM
Calixto
J B
JB
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000502:physiology; D010998:Pleurisy / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000502:physiology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C065679:icatibant; D001920:Bradykinin