Liu Y J
Department of Analytical Pharmacology, King's College School of Medicine and Dentistry, Rayne Institute, London, UK.
Eur J Pharmacol. 1993 Apr 22;235(1):9-15. doi: 10.1016/0014-2999(93)90813-w.
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.
在一项离体兔主动脉试验中，比较了三种作用于血管紧张素AT1受体的肽类似物，即[Sar1]血管紧张素II、血管紧张素II和[Asn1,Val5]血管紧张素II。已发现它们在激动剂谱以及与氯沙坦（一种对AT1受体具有选择性的非肽拮抗剂）的激动剂 - 拮抗剂相互作用方面存在显著差异。最显著的是，使用[Sar1]血管紧张素II时，Schild图呈平坦状，导致对氯沙坦拮抗剂效力的低估。这些发现通过使用包括[Sar1,Ala8]血管紧张素II在内的代表性肽拮抗剂的进一步检查得到了证实。对AT2结合位点具有选择性的非肽拮抗剂PD123177未能在[Sar1,Phe(Br5)8]血管紧张素II对血管紧张素II的复杂拮抗作用中诱导出任何显著差异，这似乎排除了AT2结合位点在观察到的激动剂之间差异以及复杂拮抗作用中发挥重要作用。基于目前的研究结果推测，可能涉及一个可饱和的激动剂清除过程或AT1受体的异质性亚群。
