Miasiro N, Oshiro M E, Paiva T B, Paiva A C
Eur J Pharmacol. 1983 Mar 4;87(4):397-406. doi: 10.1016/0014-2999(83)90078-x.
The structural requirements for the production of angiotensin tachyphylaxis in the guinea-pig ileum were studied by analyzing the tachyphylactic properties of the following synthetic analogues of angiotensin II (AII): [1-sarcosine]AII, [1-betaine]AII; [1-guanidinoacetic]AII; betainyl-AII; [2-lysine]AII; [2-ornithine]AII. In the non-atropinized ileum, no tachyphylaxis was observed with any of the following analogues: [2-lysine]AII, [2-ornithine]AII, [2-ornithine]AII, [1-betaine]AII and betainyl-AII. [1-Guanidinoacetic]AII induced tachyphylaxis, but to a smaller degree than AII, while [1-sarcosine]AII was significantly more tachyphylactic than AII. Similar results were obtained in the atropinized ileum, except that moderate tachyphylaxis was also observed with betainyl-AII and [1-betaine]AII. The analogues with lysine or ornithine residues in position 2 did not induce tachyphylaxis under any of the conditions studied. It is concluded that, besides the protonated N-terminal amino group, the guanidino group of the Arg2 side-chain is essential for the manifestation of angiotensin tachyphylaxis in the guinea-pig ileum.
通过分析以下血管紧张素II（AII）的合成类似物的快速耐受性：[1-肌氨酸]AII、[1-甜菜碱]AII、[1-胍基乙酸]AII、甜菜碱酰基-AII、[2-赖氨酸]AII、[2-鸟氨酸]AII，研究了豚鼠回肠中产生血管紧张素快速耐受性的结构要求。在未用阿托品处理的回肠中，以下任何一种类似物均未观察到快速耐受性：[2-赖氨酸]AII、[2-鸟氨酸]AII、[2-鸟氨酸]AII、[1-甜菜碱]AII和甜菜碱酰基-AII。[1-胍基乙酸]AII可诱导快速耐受性，但程度小于AII，而[1-肌氨酸]AII的快速耐受性明显高于AII。在阿托品处理的回肠中也获得了类似结果，只是甜菜碱酰基-AII和[1-甜菜碱]AII也观察到中度快速耐受性。在研究的任何条件下，2位带有赖氨酸或鸟氨酸残基的类似物均未诱导快速耐受性。结论是，除了质子化的N端氨基外，Arg2侧链的胍基对于豚鼠回肠中血管紧张素快速耐受性的表现也是必不可少的。
