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 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.
Nägler
Dorit K
DK
Division of Clinical Chemistry and Clinical Biochemistry, Surgical Department, Ludwig-Maximilians-University, Munich, Germany. dorit.naegler@med.uni-muenchen.de
Kraus
Steffen
S
Feierler
Jens
J
Mentele
Reinhard
R
Lottspeich
Friedrich
F
Jochum
Marianne
M
Faussner
Alexander
A
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007609:Kallidin / Q000378:metabolism; D016234:Kallikrein-Kinin System; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D011869:Radioligand Assay; D018000:Receptors, Peptide / Q000819:agonists*; D012084:Renin-Angiotensin System
D018000:Receptors, Peptide; D000804:Angiotensin II; D007609:Kallidin; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C534130:CTSK protein, human; D056657:Cathepsin K; D001920:Bradykinin