A possible alternative mechanism of kinin generation in vivo by cathepsin L

A possible alternative mechanism of kinin generation in vivo by cathepsin L

Author Puzer, L. Google Scholar
Vercesi, J. Google Scholar
Alves, MFM Google Scholar
Barros, NMT Google Scholar
Araujo, M. S. Google Scholar
Juliano, M. A. Google Scholar
Reis, M. L. Google Scholar
Juliano, L. Google Scholar
Carmona, A. K. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract We investigated the ability of cathepsin L to induce a hypotensive effect after intravenous injection in rats and correlated this decrease in blood pressure with kinin generation. Simultaneously with blood pressure decrease, we detected plasma kininogen depletion in the treated rats. the effect observed in vivo was abolished by preincubation of cathepsin L with the cysteine peptidase-specific inhibitor E-64 (11 mu m) or by previous administration of the bradykinin B-2 receptor antagonist JE049 (4 mg/kg). A potentiation of the hypotensive effect caused by cathepsin L was observed by previous administration of the angiotensin I-converting enzyme inhibitor captopril (5 mg/kg). in vitro studies indicated that cathepsin L excised bradykinin from the synthetic fluorogenic peptide Abz-MTSVIRRPPGFSPFRAPRV-NH2, based on the Met(375)-Val(393) sequence of rat kininogen (Abz=o-aminobenzoic acid). in conclusion, our data indicate that in vivo cathepsin L releases a kinin-related peptide, and in vitro experiments suggest that the kinin generated is bradykinin. Although it is well known that cysteine proteases are strongly inhibited by kininogen, cathepsin L could represent an alternative pathway for kinin production in pathological processes.
Keywords blood pressure decrease
bradykinin
cathepsins
inflammation
kinin
kininogen
Language English
Date 2005-07-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 386, n. 7, p. 699-704, 2005.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 699-704
Origin http://dx.doi.org/10.1515/BC.2005.081
Access rights Closed access
Type Article
Web of Science ID WOS:000230893100011
URI http://repositorio.unifesp.br/handle/11600/28382

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