Binding and signaling of angiotensin-(1-7) in bovine kidney epithelial cells involves the AT(4) receptor.
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.
Handa
R K
RK
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, 99164-6520, Pullman, WA 99164-6520, USA. Handa@vetmed.wsu.edu
D000809:Angiotensins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002413:Cations, Divalent; D002417:Cattle; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008024:Ligands; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D011945:Receptors, Angiotensin / Q000378:metabolism*
D000809:Angiotensins; D002413:Cations, Divalent; D008024:Ligands; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D020928:Mitogen-Activated Protein Kinases