Ability of kallikrein to generate angiotensin II-like pressor substance and a proposed ‘kinin–tensin enzyme system’

Abstract

Pig pancreatic kallikrein liberates kallidin from kininogen¹, whereas trypsin releases bradykinin². Recently, both kallikrein and trypsin have been reported to convert inactive plasma renin to active renin^3,4. However, we found that at pH 6.0, trypsin generated an angiotensin II-like pressor substance from human plasma protein in the absence of converting enzyme⁵. This has been isolated and found to have the same amino acid composition as angiotensin II⁶. Thus, in vitro trypsin can directly liberate both the depressor, bradykinin, in weak alkaline conditions, and the pressor, angiotensin II, at weakly acidic pH, from the appropriate substrates. We have now investigated whether kallikrein—a serine protease like trypsin—also generates a pressor substance at weakly acidic pH. Our results demonstrate that it does. We therefore suggest that kallikrein may be involved in a direct link between the pressor and depressor systems and we propose the term ‘kinin–tensin system’ for this sort of one-enzyme system capable of generating both depressor and pressor substances.