Abstract：
Alamandine is a peptide hormone belonging to the renin-angiotensin system (RAS). It acts through the Mas-related G-protein coupled receptor type D, MrgD, which is expressed in different tissues, including the brain. In the present study, we hypothesize that a lack of alamandine, through MrgD, could cause the anxiety-like behavior in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)680]. Adult male transgenic rats exhibited a significant increase in the latency to feeding time in the novelty suppressed feeding test and a decrease in the percentage of time and entries in the open arms in the elevated plus maze. These effects were reversed by intracerebroventricular infusion of alamandine. Pretreatment with D-Pro7-Ang-(1-7), a Mas and MrgD receptor antagonist, prevented the anxiolytic effects induced by this peptide. However, its effects were not altered by the selective Mas receptor antagonist, A779. In conclusion, our data indicates that alamandine, through MrgD, attenuates anxiety-like behavior in male TGR(ASrAOGEN)680, which reinforces the importance of the counter-regulatory RAS axis as promising target for the treatment of neuropsychiatric disorders.
摘要：
Alamandine是属于肾素-血管紧张素系统（RAS）的肽激素。它通过Mas相关的D型G蛋白偶联受体起作用，MrgD,在不同的组织中表达，包括大脑。在本研究中,我们假设缺乏alamandine，通过MrgD,在低脑血管紧张素原[TGR（ASrAOGEN）680]的转基因大鼠中可能引起焦虑样行为。在新颖性抑制喂养测试中，成年雄性转基因大鼠的喂养时间潜伏期显着增加，而在高架迷宫中开放臂的时间百分比和进入时间百分比减少。通过脑室内输注alamandine可以逆转这些作用。用D-Pro7-Ang-（1-7）预处理，Mas和MrgD受体拮抗剂，预防了该肽诱导的抗焦虑作用。然而,它的作用没有被选择性Mas受体拮抗剂改变，A779.总之,我们的数据表明Alamandine,通过MrgD,减轻男性TGR（ASrAOGEN）680的焦虑样行为，这加强了反调节RAS轴作为治疗神经精神疾病的有希望的目标的重要性。
