Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15 A, 15274 Bialystok, Poland.
Neurosci Biobehav Rev. 2010 Mar;34(3):343-50. doi: 10.1016/j.neubiorev.2009.08.001. Epub 2009 Aug 15.
Angiotensin IV (Ang IV) and des-Phe(6)Ang IV are naturally occurring neuroactive peptides of the renin-angiotensin system (RAS) involved in memory processing. However, the relevant mechanisms are poorly understood. In this review it is proposed that the pro-cognitive effects of these peptides are, at least partly, mediated by dopamine (DA). Recent studies demonstrated that the improvement of several memory aspects; recall of appetitively and aversively motivated behaviors and learning of spatial tasks by Ang IV and des-Phe(6)Ang IV was abolished, or significantly diminished by behaviorally inactive per se doses of the D(1) and D(2) receptor blockers SCH 23390 (R-[+]-7-chloro-8-hydroxy-3 methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and remoxipride, respectively. The D(3) receptor inhibition with nafadotride was almost ineffective but again, the D(4) receptor blockade by L745,870 hydrochloride (3-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine hydrochloride) diminished all, except for spatial memory, improving actions of the peptides. These results suggest that Ang IV and des-Phe(6)Ang IV enhance memory in a brain region-specific manner, dependent on local DA receptor subpopulations and the memory aspects controlled by them. The data reviewed here, demonstrating DA-Ang IV and des-Phe(6)Ang IV interactions in brain, strongly suggest probability of clinically relevant effects of concomitant use of antipsychotic and RAS affecting drugs.
血管紧张素 IV（Ang IV）和去苯丙氨酸 6 血管紧张素 IV（des-Phe6Ang IV）是肾素-血管紧张素系统（RAS）中天然存在的神经活性肽，参与记忆处理。然而，相关机制尚不清楚。在这篇综述中，提出这些肽的促认知作用至少部分是通过多巴胺（DA）介导的。最近的研究表明，Ang IV 和 des-Phe6Ang IV 改善了几种记忆方面；食欲和厌恶动机行为的回忆以及空间任务的学习，而 D1 和 D2 受体阻滞剂 SCH 23390（R-[+]-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓）和 remoxipride 分别以行为上无活性的自身剂量给药时，其改善作用被消除或显著减弱。D3 受体抑制作用用 nafadotride 几乎无效，但再次，D4 受体阻断剂 L745,870 盐酸盐（3-{[4-（4-氯苯基）哌嗪-1-基]甲基}-1H-吡咯并[2,3-b]吡啶盐酸盐）除空间记忆外，均减弱了所有肽的改善作用。这些结果表明，Ang IV 和 des-Phe6Ang IV 以脑区特异性方式增强记忆，依赖于局部 DA 受体亚群及其控制的记忆方面。这里综述的数据表明，DA-血管紧张素 IV 和 des-Phe6Ang IV 之间在大脑中的相互作用，强烈表明同时使用抗精神病药和影响 RAS 的药物具有临床相关影响的可能性。
