Braszko J J, Kułakowska A, Karwowska-Polecka W
Clinical Pharmacology Unit, Medical Academy of Białystok, Poland.
Pharmacol Res. 1998 Dec;38(6):461-8. doi: 10.1006/phrs.1998.0395.
An involvement of the angiotensin AT2 receptors in some behavioural effects of angiotensin II (Ang II) and its 3-7 fragment [Ang II(3-7)] in rats was studied. To inhibit AT2 receptors we used their selective antagonist CGP 42112A (nicotinic acid-Tyr-N-benzoxyl-carbonyl-Arg-Lys-His-Pro-Ile-OH). Ang II and Ang II(3-7), given intracerebroventricularly (i.c.v.) at the dose of 1 nmol each, significantly enhanced recall of the passive avoidance behaviour and learning of the conditioned avoidance responses (CARs). CGP 42112A (2 micrograms i.c.v.), inactive on its own in all tests, significantly attenuated facilitation of recall of passive avoidance caused by Ang II and Ang II(3-7). Also, CGP 42112A diminished Ang II improvement of CARs acquisition but not that caused by Ang II(3-7). None of the treatments produced significant anxiolysis in an elevated 'plus' maze. Likewise, in an open field no statistically significant differences were recorded except for the abolishment of the Ang II(3-7)-induced increase of rearings and bar approaches by CGP 42112A. It appears that the cognition improving activity of Ang II and Ang II(3-7) is mediated by similar mechanisms and angiotensin AT2 receptors are engaged in these processes.
研究了血管紧张素AT2受体在血管紧张素II(Ang II)及其3 - 7片段[Ang II(3 - 7)]对大鼠某些行为影响中的作用。为抑制AT2受体,我们使用了其选择性拮抗剂CGP 42112A(烟酸 - 酪氨酸 - N - 苄氧基羰基 - 精氨酸 - 赖氨酸 - 组氨酸 - 脯氨酸 - 异亮氨酸 - 羟基)。分别以1 nmol的剂量脑室内注射(i.c.v.)Ang II和Ang II(3 - 7),可显著增强被动回避行为的记忆及条件性回避反应(CARs)的学习。CGP 42112A(2微克i.c.v.)在所有测试中自身无活性,但能显著减弱Ang II和Ang II(3 - 7)引起的被动回避记忆增强作用。此外,CGP 42112A减弱了Ang II对CARs获得的促进作用,但对Ang II(3 - 7)引起的促进作用无影响。在高架“十”字迷宫中,所有处理均未产生显著的抗焦虑作用。同样,在旷场实验中,除CGP 42112A消除了Ang II(3 - 7)引起的竖毛和接近横杆次数增加外,未记录到统计学上的显著差异。看来,Ang II和Ang II(3 - 7)改善认知的活性是由相似机制介导的,且血管紧张素AT2受体参与了这些过程。