A cysteine-type carboxypeptidase, cathepsin X, generates peptide receptor agonists

The kallikrein–kinin system and the renin–angiotensin system interact at different levels and are linked by various molecules such as angiotensin-converting enzyme which degrades bradykinin into inactive peptides. Here we report that a cysteine-type carboxypeptidase, cathepsin X, is able to modulate the kallikrein–kinin system through carboxyterminal processing of the small peptide hormones bradykinin and kallidin. Both peptides are thereby converted from bradykinin B2 receptor ligands to bradykinin B1 receptor specific ligands. Cathepsin X, which has previously been recognized as an inflammatory marker may therefore act as a type I kininase. In addition, we have identified cathepsin X as an alternative possible link between the kallikrein–kinin system and the renin–angiotensin system in that it not only cleaves kinins C-terminally, but also converts angiotensin I to angiotensin II.