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  • Title: Angiotensin-[1-12] interacts with angiotensin type I receptors.
    Author: Chan KH, Chen YH, Zhang Y, Wong YH, Dun NJ.
    Journal: Neuropharmacology; 2014 Jun; 81():267-73. PubMed ID: 23823979.
    Abstract:
    Angiotensin-(1-12) [Ang-(1-12)], a newer member of angiotensin peptides, is proposed to be converted enzymatically to angiotensin I (Ang I) and to angiotensin II (Ang II); the latter being the bioactive peptide. We studied the Ang-(1-12) and Ang II responses in COS-7 cells or CHO cells transfected with 5 μg AT1R by monitoring [Ca(2+)]i using the Fluo-4. Ang II (1 pM-1 μM) and Ang-(1-12) (5 pM-5 μM) increased [Ca(2+)]i with an EC50 of 0.19 nM and 24 nM in COS-7 cells; and 0.65 nM and 28.7 nM in CHO cells. The AT1R antagonist losartan (1 nM-10 μM) suppressed [Ca(2+)]i induced by Ang-(1-12) and Ang II. In CHO cells transfected with 5 μg AT2R, Ang II (1 pM-1 μM) increased [Ca(2+)]i, with an EC50 of 9.68 nM; whereas, Ang-(1-12) (5 pM-5 μM) failed to elicit a significant change in [Ca(2+)]i. In CHO cells transfected with AT1R, Ang-(1-12) stimulated ERK phosphorylation with a potency 300-fold less than that of Ang II. To evaluate the activity of Ang-(1-12) on native AT1R, whole cell patch recordings were made from neurons in the rat hypothalamic slices. Ang II or Ang-(1-12) ejected by pressure from a micropipette elicited a membrane depolarization; the latter was blocked by losartan (10 μM), and not affected by the AT2R antagonist PD123319 (10 μM), nor by the angiotensin converting enzyme inhibitor captopril (10 μM). Our result shows that Ang-(1-12) may produce its biological activity by acting directly on AT1R, albeit at a concentration higher than that of Ang II.
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