Lack of Intra-cellular Signalling by Angiotensin IV in IRAP Transfected Cells |
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Authors: | Anthony L. Albiston Vi Pham Siew Yeen Chai |
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Affiliation: | (1) Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, VIC, 3010, Australia;(2) Centre for Neuroscience, Parkville, VIC, 3010, Australia |
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Abstract: | A number of studies have suggested that angiotensin IV is able to mediate a range of signalling events through a receptor distinct to the well-characterised angiotensin AT1 and AT2 receptors. This receptor was termed the AT4 receptor, but was subsequently identified to be the transmembrane enzyme, insulin regulated aminopeptidase, IRAP. Using HEK293T cells transfected with IRAP we investigated whether angiotensin IV was able to mediate signalling events via this aminopeptidase. No effect of the angiotensin IV analogue, Nle1-Ang IV, on intracellular calcium or ERK phosphorylation was observed. In addition, the effect of Nle1-Ang IV on IRAP internalization was investigated and, in contrast to classical ligand-mediated receptor endocytosis, Nle1-Ang IV (10−6 M) extends the half-life of IRAP at the plasma membrane. Our results do not support a direct role for Ang IV signalling via IRAP in this system. |
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Keywords: | AT4 receptor Ang IV angiotensin IRAP |
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