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(Hypertension. 2008;51:689.)
© 2008 American Heart Association, Inc.

Original Articles

ACE Activity Is Modulated by Kinin B₂ Receptor

Regiane A. Sabatini; Paola B. Guimarães; Liliam Fernandes; Felipe C.G. Reis; Patricia A. Bersanetti; Marcelo A. Mori; Alberto Navarro; Aline M. Hilzendeger; Edson L. Santos; Maria C.C. Andrade; Jair R. Chagas; Jorge L. Pesquero; Dulce E. Casarini; Michael Bader; Adriana K. Carmona; João B. Pesquero

From the Department of Biophysics (R.A.S., P.B.G., L.F., F.C.G.R., P.A.B., M.A.M., A.N., A.M.H., E.L.S., A.K.C., J.B.P.), Nephrology Division, Department of Medicine (M.C.C.A., D.E.C.), and Department of Psychobiology (J.R.C.), Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil; the Department of Physiology and Biophysics (J.L.P.), Federal University of Minas Gerais, Belo Horizonte, Brazil; and the Molecular Biology of Peptide Hormones Group (M.B.), Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.

Correspondence to João B. Pesquero, Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, 04023-062 São Paulo, Brazil. E-mail jbpesq{at}biofis.epm.br

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 B₂ 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 B₂ receptor leads to an augmentation in ACE activity. In addition, this effect could be blocked by the B₂ 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 B₂ 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 B₂ 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.

Key Words: ACE • kinin B₂ receptor • dimerization • enzyme activity • ACE inhibitors • icatibant