Authors
Titiwat Sungkaworn, Chutima Jiarpinitnun, Pongkorn Chaiyakunvat, Varanuj Chatsudthipong
Publication date
2013/5/1
Journal
European Journal of Medicinal Chemistry
Volume
63
Pages
629-634
Publisher
Elsevier Masson
Description
Angiotensin II receptor type I (AT1R) is a G-protein coupled receptor involved in regulation of body water-electrolyte balance and blood pressure. Oxidative stress promotes AT1R oligomerization and hyper-responsiveness to its cognate ligand Ang II. In this study, bivalent Ang II, synthesized by linking with aminocaproic acid (Acp) at the N-terminus, was used to induce AT1R dimerization and hyper-responsiveness in AT1R-expressed human embryonic kidney (AT1R-HEK) cells, determined using image correlation spectroscopy (ICS) and by measuring AT1R-mediated change in intracellular Ca2+ concentration, respectively. In addition, ICS was employed to determine distribution pattern of cell-surface AT1R and its degree of aggregation when stimulated by monomeric (monovalent) and bivalent Ang II under oxidative stress (100 μM H2O2) condition in comparison with normal (unoxidized) AT1R-HEK cells. Bivalent …
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