Binding and signaling of angiotensin-(1-7) in bovine kidney epithelial cells involves the AT(4) receptor |
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Authors: | Handa R K |
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Institution: | Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, 99164-6520, Pullman, WA 99164-6520, USA. Handa@vetmed.wsu.edu |
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Abstract: | Angiotensin-(1-7) decreased mitogen-activated protein (MAP) kinase (Erks) activation in cultured Mardin-Darby bovine kidney (MDBK) epithelial cells. Also, saturable, high-affinity (125)I-angiotensin-(1-7) binding was detected in MDBK cell membranes. Together, the data suggested the possible presence of an angiotensin-(1-7) receptor. However, ligand structure-binding studies revealed that angiotensin-(3-7) and AT(4) receptor ligands competed with high-affinity for (125)I-angiotensin-(1-7) binding. Furthermore, angiotensin-(3-7) and AT(4) receptor ligands decreased MAP kinase activation in MDBK cells. These results demonstrate that NH(2)-terminal-deleted metabolites of angiotensin-(1-7) can bind with high affinity to the AT(4) receptor and regulate the MAP kinase/Erk signaling pathway in renal epithelial cells. |
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