Oshiro M E, Shimuta S I, Paiva T B, Paiva A C
Department of Biophysics, Escola Paulista de Medicina, Sao Paulo, SP, Brazil.
Eur J Pharmacol. 1989 Aug 3;166(3):411-7. doi: 10.1016/0014-2999(89)90353-1.
The homologous desensitization induced by angiotensin II analogues in the guinea-pig isolated ileum was studied. Desensitization assessed by the loss of response on repeated treatment showed [Sar1]angiotensin II to be a strong desensitizer whereas no desensitization to [Lys2]angiotensin II was detected. However, prolonged treatment with either analogue desensitized the tissue, indicating that [Lys2]angiotensin II-induced desensitization was reversed faster. A correlation was found between the degree of desensitization caused by repeated treatment and the time for half-relaxation after washout of the first treatment, but the relaxation after washout became faster in the desensitized state. In experiments designed to study competition between the agonistic and desensitizing properties of angiotensin II analogues, high concentrations of [Lys2]angiotensin II blocked the agonistic but not the desensitizing effect of lower concentrations of [Sar1]angiotensin II. It is concluded that desensitization is due to the interaction of angiotensin II with a regulatory site on the receptor.
研究了血管紧张素 II 类似物在豚鼠离体回肠中诱导的同源脱敏作用。通过重复给药后反应丧失评估的脱敏作用表明，[Sar1]血管紧张素 II 是一种强效脱敏剂，而未检测到对[Lys2]血管紧张素 II 的脱敏作用。然而，用任何一种类似物进行长时间处理都会使组织脱敏，这表明[Lys2]血管紧张素 II 诱导的脱敏作用恢复得更快。发现重复给药引起的脱敏程度与第一次给药洗脱后的半松弛时间之间存在相关性，但在脱敏状态下洗脱后的松弛变得更快。在旨在研究血管紧张素 II 类似物的激动和脱敏特性之间竞争的实验中，高浓度的[Lys2]血管紧张素 II 阻断了低浓度[Sar1]血管紧张素 II 的激动作用，但未阻断其脱敏作用。得出的结论是，脱敏是由于血管紧张素 II 与受体上的调节位点相互作用所致。
