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

Abstract 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 B 2 receptor ligands to bradykinin B 1 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.