Edematous response caused by [Thi5,8,D-Phe7]bradykinin, a B2 receptor antagonist, is due to mast cell degranulation.
[Thi5,8,D-Phe7]bradykinin caused hind-paw edema and degranulation of isolated peritoneal mast cells in a dose-dependent manner. Pretreatment with diphenhydramine/methysergide or compound 48/80 completely suppressed the edematous response caused by [Thi5,8,D-Phe7]bradykinin, whereas bradykinin-induced hind-paw swelling was only partially inhibited by diphenhydramine and methysergide pretreatment; the residual response was significantly further depressed by [Thi5,8,D-Phe7]bradykinin. Neither the bradykinin- nor [Thi5,8,D-Phe7]bradykinin-induced edematous response was significantly affected by aspirin or BW755C. The mast cell degranulation caused by [Thi5,8,D-Phe7]bradykinin and bradykinin was inhibited by gangliosides but not by heparin. These results suggest that the edematous response elicited by [Thi5,8,D-Phe7]bradykinin was mainly due to the actions of mediators released by the degranulation of mast cells. Unlike bradykinin, [Thi5,8,D-Phe7]bradykinin was devoid of a direct exudation-promoting effect but exerted an antagonistic effect on the direct effect of kinin. If the influence of mast cells degranulation could be minimized, [Thi5,8,D-Phe7]bradykinin could be used as a tool to evaluate the role of kinin in the edematous response in inflammation.
Wang
J P
JP
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsu
M F
MF
Ouyang
C H
CH
Teng
C M
CM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced*; D005966:Glucuronidase / Q000378:metabolism; D006632:Histamine / Q000502:physiology; D008407:Mast Cells / Q000187:drug effects / Q000648:ultrastructure*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012701:Serotonin; D006632:Histamine; C053426:bradykinin, (Thi-Ala)(5,8)-Phe(7)-; D005966:Glucuronidase; D001920:Bradykinin