Differential bradykinin B-1 and B-2 receptor regulation in cell death induced by hepatic ischaemia/reperfusion injury

Differential bradykinin B-1 and B-2 receptor regulation in cell death induced by hepatic ischaemia/reperfusion injury

Author Paio, Mayra de Almeida Autor UNIFESP Google Scholar
Kouyoumdjian, Maria Autor UNIFESP Google Scholar
Borges, Durval R. Autor UNIFESP Google Scholar
Nagaoka, Marcia Regina Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract The biological and pharmacological effects of BK (bradykinin) are mediated by two receptors: the constitutive B2R (B-2 receptor) and the inducible B1R (B-1 receptor). BK plays a role in the hepatic microcirculation by inducing the PHR (portal hypertensive response) via B2R, whereas DABK (des-Arg(9)-BK), a B1R agonist, does not elicit the response. During IRI (ischaemia/reperfusion injury), important changes occur in the microcirculation, and cell death by necrosis and apoptosis is involved in poor graft function. the aim of the present study was to analyse the role of B1R and B2R in liver cell death induced by IRI. Livers from Wistar rats were submitted to ischaemia (4 degrees C) for 4 or 24 h. After this period, livers were reperfused ex vivo with Krebs Henseleit solution (37 degrees C). BK or DABK was then injected as a bolus during reperfusion in the absence or presence of HOE-140 (a B2R antagonist) or DALBK (des-Arg(9)-Leu(9)-BK) (a B1R antagonist) respectively. Liver viability was analysed by glucose release and bile secretion. the PHR to kinins did not change. Cell death was higher in the DABK group and its antagonist significantly decreased cell death. Interestingly, the B1R antagonist did not alter the number of necrotic cells, but it decreased the number of apoptotic cells. On the other hand, the B2R antagonist decreased the number of necrotic cells, but did not alter the number of apoptotic cells. Therefore B1R may participate in apoptotic cell death signalling, and B2R may be involved in necrotic cell death.
Keywords apoptosis
bradykinin
ischaemia/reperfusion injury
kinin
liver
necrosis
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: MRN 08/55928-0
FAPESP: MAP 08/08916-6
CNPq: 477869/2008-4
CNPq: 300045/2010-7
Date 2014-09-01
Published in Clinical Science. London: Portland Press Ltd, v. 127, n. 5-6, p. 405-413, 2014.
ISSN 0143-5221 (Sherpa/Romeo, impact factor)
Publisher Portland Press Ltd
Extent 405-413
Origin http://dx.doi.org/10.1042/CS20130313
Access rights Closed access
Type Article
Web of Science ID WOS:000339859900012
URI http://repositorio.unifesp.br/handle/11600/38182

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