ACTIVATION BY PHONEUTRIA-NIGRIVENTER (ARMED SPIDER) VENOM OF TISSUE KALLIKREIN-KININOGEN-KININ SYSTEM IN RABBIT SKIN INVIVO

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 I-125-labelled human serum albumin into skin sites. 3 Phoneutria nigriventer venom (10-30 mug/site) increased vascular permeability, which was inhibited by trasylol (10 mug/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 mug/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.