Homologous tachyphylaxis to bradykinin and its interference with allergic pleurisy in actively sensitized rats.
After recovery from a first intraplantar or intrathoracic stimulation with bradykinin, repeated daily provocation with this peptide resulted in a progressive loss of its ability to cause paw or pleural oedema, reaching 0-20% of the control within seven and four consecutive provocations, respectively. The phenomenon was shown to be time reversible, since the unresponsiveness ceased when stimulations were discontinued, and localized, since paw oedema evoked by the peptide was not modified after desensitization of either the contralateral paw or the pleural cavity. Furthermore desensitization to bradykinin did not influence the pleurisy elicited by either histamine (200 micrograms/cavity), 5-hydroxytryptamine (5-HT) (100 microgram/cavity) or platelet-activating factor (PAF) (1 microgram/cavity), suggesting that the desensitization was selective. In contrast, when actively sensitized animals were submitted to bradykinin-induced tachyphylaxis, pleural exudation and leukocyte influx induced by antigen were drastically reduced, strongly implying bradykinin in this process. We demonstrated that repeated daily stimulation with bradykinin cause selective, local and reversible auto-refractoriness, which may be useful as a tool in attempting to evaluate the role of this peptide in inflammation.
Martins
M A
MA
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Pasquale
C P
CP
Bozza
P T
PT
Silva
P M
PM
Faria Neto
H C
HC
COrdeiro
R S
RS
D000595:Amino Acid Sequence; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010998:Pleurisy / Q000276:immunology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013618:Tachyphylaxis; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004224:Diterpenes; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D014230:Triazoles; C052518:WEB 2086; D010047:Ovalbumin; C045856:ginkgolide B; D001920:Bradykinin