Effect of Neurotropin on the activation of the plasma kallikrein-kinin system.
Bradykinin (BK), an important mediator of allergic reactions and pain induction, is released by the activation of the plasma kallikrein-kinin (K-K) cascade. Neurotropin is a biological material obtained from inflamed rabbit skin inoculated with vaccinia virus and is widely used clinically in Japan as an effective agent for these disorders. Since its mechanism of action is not clearly known, we have investigated the effects of Neurotropin on the human plasma K-K system. In dextran sulfate-activated plasma, Neurotropin inhibited the formation of BK, the cleavage of high molecular weight kininogen (HK) and the formation of kallikrein-C1 inhibitor and activated coagulation factor XII (FXIIa)-C1 inhibitor complexes. Experiments using purified enzyme of the K-K cascade indicated that Neurotropin inhibited surface-mediated activation of coagulation factor XII (FXII) and the activation of prekallikrein by FXIIa. Neurotropin also inhibited the binding of FXII and HK to the activating surface. These data suggest that the ameliorating effects of Neurotropin in allergic disorders and pain syndromes may be related to this ability to inhibit activation of the K-K cascade and consequently the formation of BK.
Nishikawa
K
K
Department of Medicine, State University of New York, Stony Brook 11794-8161.
Reddigari
S R
SR
Silverberg
M
M
Kuna
P B
PB
Yago
H
H
Nagaki
Y
Y
Toyomaki
Y
Y
Suehiro
S
S
Kaplan
A P
AP
D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016264:Dextran Sulfate; D004789:Enzyme Activation / Q000187:drug effects; D005174:Factor XII / Q000037:antagonists & inhibitors; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D007610:Kallikreins / Q000302:isolation & purification / Q000378:metabolism*; D007616:Kaolin / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D011288:Prekallikrein / Q000302:isolation & purification; D011817:Rabbits
D007704:Kininogens; D009842:Oligopeptides; D011134:Polysaccharides; D007616:Kaolin; C010491:neurotropin; C031694:Chromozym PK; D005174:Factor XII; D016264:Dextran Sulfate; D011288:Prekallikrein; D007610:Kallikreins; D001920:Bradykinin