Vespula vulgaris venom: role of kinins and release of 5-hydroxytryptamine from skin mast cells.
Wasp venoms contain several active components, among them kinin-related peptides. Like bradykinin and [Thr6]bradykinin, Vespula vulgaris venom caused paw oedema following subplantar injection in anaesthetized rats. The oedema was partly inhibited by the bradykinin B2 receptor antagonist icatibant (Hoe 140); the remaining part was abolished by additional pretreatment with 5-hydroxytryptamine (5-HT) receptor antagonists or mast cell depletion. Histamine receptor antagonists were ineffective. Capsaicin pretreatment attenuated oedema formation indicating a neurogenic sensory component. Nociceptive behavioural responses induced by the venom in unanaesthetized rats were abolished by icatibant. It is concluded that kinins, either contained in the venom or released from the tissue, play the predominant role in the inflammatory and algesic effects. The inflammatory effects only partly rely on direct, bradykinin receptor-mediated mechanisms while the remaining part depends on the release of 5-HT from skin mast cells. The algesic effects of the venom are entirely due to direct B2 receptor activation.
Department of Experimental and Clinical Pharmacology, University of Graz, Austria. thomas.griesbacher@kfunigraz.ac.at
T
T
Griesbacher
P
P
Althuber
M
M
Zenz
I
I
Rainer
S
S
Griengl
F
F
Lembeck
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D002211:Capsaicin / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007705:Kinins / Q000032:analysis / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects; D014862:Wasp Venoms / Q000737:chemistry / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007705:Kinins; D043782:Receptor, Bradykinin B2; D012702:Serotonin Antagonists; D014862:Wasp Venoms; D012701:Serotonin; C065679:icatibant; D002211:Capsaicin; D001920:Bradykinin