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  • Title: Evidence that [Sar1]angiotensin II behaves differently from angiotensin II at angiotensin AT1 receptors in rabbit aorta.
    Author: Liu YJ.
    Journal: Eur J Pharmacol; 1993 Apr 22; 235(1):9-15. PubMed ID: 8519284.
    Abstract:
    Three peptide analogues, [Sar1]angiotensin II, angiotensin II and [Asn1, Val5]angiotensin II, that act at angiotensin AT1 receptors were compared in an isolated rabbit aorta assay. Significant differences have been found among them in agonist profiles and agonist-antagonist interactions with losartan, a nonpeptide antagonist selective for AT1 receptors. Most significantly, underestimation of the antagonist potency for losartan with a flat Schild plot was obtained with [Sar1]angiotensin II. These findings were confirmed in further examinations with representative peptide antagonists including [Sar1,Ala8]angiotensin II. The failure of PD123177, a nonpeptide antagonist selective for AT2 binding sites, to induce any significant difference in the complex antagonism of [Sar1,Phe(Br5)8]angiotensin II to angiotensin II appeared to rule out significant involvement of AT2 binding sites in the differences observed among the agonists, as well as in the complex antagonism. On the basis of the present findings it is speculated that either a saturable agonist removal process or heterogeneous sub-populations of AT1 receptors may be involved.
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