ACTIVATION OF TISSUE KALLIKREIN-KININOGEN-KININ SYSTEM IN RABBIT SKINBY A FRACTION ISOLATED FROM PHONEUTRIA-NIGRIVENTER (ARMED SPIDER) VENOM

Phoneutria nigriventer venom was fractionated by gel filtration follow ed by ion-exchange chromatography from which 16 fractions (I-XVI) were obtained and assayed in rabbit skin in order to identify those respon sible for the increased vascular permeability observed with the whole venom. The fractions, and control mediators (tissue kallikrein, bradyk inin and histamine) were intradermally injected in male New Zealand wh ite rabbits. Local oedema formation was measured as the local accumula tion of i.v. injected I-125-human serum albumin into skin sites. Fract ion XIII was the only fraction assayed which significantly induced oed ema formation. Fraction XIII-induced oedema was greatly reduced by eit her the protease inhibitor aprotinin or the bradykinin B2 receptor ant agonist D-Arg,[Hyp3,Thi5.8,D-Phe7]-Bk, whereas the plasma kallikrein i nhibitor soybean trypsin inhibitor failed to significantly affect this oedematogenic response. The kininase II inhibitor captopril markedly potentiated fraction XIII-induced oedema. Our results indicate that th e increased vascular permeability induced by fraction XIII is due to l ocal generation of kinins in response to tissue (but not plasma) kalli krein-kinin system activation.