Possible physiological role of new peptide fragments released from bovine high molecular weight kininogen by plasma kallikrein

Abstract

The possibility of a physiological role for two new peptides, Fragment 1.2 and Fragment 2 (histidine-rich peptide), released from bovine plasma high molecular weight (HMW) kininogen by the action of plasma kallikrein was examined. The former peptide, which was liberated at the same rate as bradykinin, and the latter peptide, which was derived from Fragment 1.2 on subsequent incubation with plasma kallikrein, showed negligible kinin-like activities. However, the peptides strongly inhibited kinin formation in bovine plasma exposed to glass ballotini, and prolonged the calcium clotting-time of citrated rat plasma in a manner similar to hexadimethrine bromide. Also, they inhibited the activation of Hageman factor by kaolin. The above three types of experiments showed the potency of Fragment 1.2 to be approximately three times that of Fragment 2 on a molar basis. Neither fragment showed inhibition of already activated Hageman factor, nor of the esterase activities of plasma kallikrein, plasmin and thrombin. These results suggest that liberation of these polypeptides from HMW kininogen represents a negative feedback mechanism for the contact activation of Hageman factor.