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ACE activity is modulated by kinin B-2 receptor

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Date
2008-03-01
Author
Sabatini, Regiane Angelica [UNIFESP]
Guimarães, Paola Bianchi [UNIFESP]
Fernandes, Liliam [UNIFESP]
Reis, Felipe Castellani Gomes dos [UNIFESP]
Bersanetti, Patricia Alessandra [UNIFESP]
Mori, Marcelo Alves da Silva [UNIFESP]
Navarro, Alberto [UNIFESP]
Hilzendeger, Aline Mourão [UNIFESP]
Santos, Edson Lucas dos [UNIFESP]
Andrade, Maria C. C. [UNIFESP]
Chagas, Jair Ribeiro [UNIFESP]
Pesquero, Jorge L.
Casarini, Dulce Elena [UNIFESP]
Bader, Michael [UNIFESP]
Carmona, Adriana Karaoglanovic [UNIFESP]
Pesquero, João Bosco [UNIFESP]
Type
Artigo
ISSN
0194-911X
Is part of
Hypertension
DOI
10.1161/HYPERTENSIONAHA.107.091181
Metadata
Show full item record
Abstract
Angiotensin-converting enzyme (ACE) is an ectoprotein able to modulate the activity of a plethora of compounds, among them angiotensin I and bradykinin. Despite several decades of research, new aspects of the mechanism of action of ACE have been elucidated, expanding our understanding of its role not only in cardiovascular regulation but also in different areas. Recent findings have ascribed an important role for ACE/kinin B-2 receptor heterodimerization in the pharmacological properties of the receptor. in this work, we tested the hypothesis that this interaction also affects ACE enzymatic activity. ACE catalytic activity was analyzed in Chinese hamster ovary cell monolayers coexpressing the somatic form of the enzyme and the receptor coding region using as substrate the fluorescence resonance energy transfer peptide Abz-FRK(Dnp) P-OH. Results show that the coexpression of the kinin B-2 receptor leads to an augmentation in ACE activity. in addition, this effect could be blocked by the B-2 receptor antagonist icatibant. the hypothesis was also tested in endothelial cells, a more physiological system, where both proteins are naturally expressed. Endothelial cells from genetically ablated kinin B-2 receptor mice showed a decreased ACE activity when compared with wild-type mice cells. in summary, this is the first report showing that the ACE/kinin B-2 receptor interaction modulates ACE activity. Taking into account the interplay among ACE, ACE inhibitors, and kinin receptors, we believe that these results will shed new light into the arena of the controversial search for the mechanism controlling these interactions.
Citation
Hypertension. Philadelphia: Lippincott Williams & Wilkins, v. 51, n. 3, p. 689-695, 2008.
Keywords
ACE
kinin B-2 receptor
dimerization
enzyme activity
ACE inhibitors
icatibant
URI
http://repositorio.unifesp.br/handle/11600/30465
Collections
  • Em verificação - Geral [10974]

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