ACE Activity Is Modulated by Kinin B2 Receptor

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2008-03, Vol.51 (3), p.689-695
• Main Authors: Sabatini, Regiane A, Guimarães, Paola B, Fernandes, Liliam, Reis, Felipe C.G, Bersanetti, Patricia A, Mori, Marcelo A, Navarro, Alberto, Hilzendeger, Aline M, Santos, Edson L, Andrade, Maria C.C, Chagas, Jair R, Pesquero, Jorge L, Casarini, Dulce E, Bader, Michael, Carmona, Adriana K, Pesquero, João B
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive agents; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Bradykinin B2 Receptor Antagonists; Cardiology. Vascular system; Cardiovascular system; Cells, Cultured; CHO Cells; Cricetinae; Cricetulus; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Female; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovary - drug effects; Ovary - metabolism; Ovary - pathology; Peptidyl-Dipeptidase A - metabolism; Pharmacology. Drug treatments; Receptor, Bradykinin B2 - genetics; Receptor, Bradykinin B2 - metabolism; Transfection
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.107.091181

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.