Activation by Phoneutria nigriventer (armed spider) venom of tissue kallikrein-kininogen-kinin system in rabbit skin in vivo.
1. The purpose of the present study was to investigate the mechanisms by which venom from Phoneutria nigriventer spider induces increases in vascular permeability in rabbit skin. 2. Local oedema formation, in response to intradermally-injected agents, was measured in male New Zealand white rabbits as the local accumulation of i.v. injected 125I-labelled human serum albumin into skin sites. 3. Phoneutria nigriventer venom (10-30 micrograms/site) increased vascular permeability, which was inhibited by trasylol (10 micrograms/site) and the bradykinin B2 receptor antagonists D-Arg,[Hyp3,Thi5,8,D-Phe7]-BK (3 nmol/site) and Hoe 140 (0.3 nmol/site). In addition, the oedema induced by the venom was potentiated by the kinase II inhibitor, captopril (1 nmol/site). The lipoxygenase inhibitor, BWA4C (10 nmol/site) and the PAF antagonist, WEB 2086 (100 nmol/site) had no effect on the venom-induced increase in vascular permeability. 4. Incubation of rabbit plasma with Phoneutria nigriventer venom in vitro did not cause bradykinin formation. Further, the plasma kallikrein inhibitor, soybean trypsin inhibitor (10 micrograms/site), had no effect on the venom-induced increase in vascular permeability in rabbit skin. 5. These results indicate that the oedema produced by Phoneutria nigriventer venom is dependent on the activation of the tissue kallikrein-kinin system.
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas, São Paulo, Brazil.
R A
RA
Marangoni
E
E
Antunes
S D
SD
Brain
G
G
de Nucci
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004487:Edema / Q000378:metabolism / Q000503:physiopathology; D006632:Histamine / Q000494:pharmacology; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007704:Kininogens / Q000502:physiology*; D008297:Male; D011817:Rabbits; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology*
D007704:Kininogens; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D013111:Spider Venoms; D006632:Histamine; D002216:Captopril; D007610:Kallikreins; D000527:Alprostadil; D001920:Bradykinin