Angiotensin-(1–7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas

• Published in: Molecular and cellular neuroscience Vol. 29; no. 3; pp. 427 - 435
• Main Authors: Hellner, K., Walther, T., Schubert, M., Albrecht, D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2005
• Subjects: Angiotensin I - metabolism; Angiotensin I - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Dose-Response Relationship, Drug; Electric Stimulation; Enzyme Inhibitors - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Learning - drug effects; Learning - physiology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Memory - drug effects; Memory - physiology; Mice; Mice, Knockout; Neurons - drug effects; Neurons - metabolism; Organ Culture Techniques; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Proto-Oncogene Proteins - drug effects; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptor, Angiotensin, Type 1 - metabolism; Receptors, G-Protein-Coupled - drug effects; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2005.03.012

The renin–angiotensin system not only plays a critical role in blood pressure control but is also involved in learning and memory mechanisms. In addition to angiotensin (Ang) II, Ang-(1–7) may also have important biological activities in the brain. Here, we show for the first time that Ang-(1–7) enhances long-term potentiation (LTP) in the CA1 region of the hippocampus. Our studies with AT1 receptor antagonists and selective Ang-(1–7) receptor antagonists demonstrate the existence of a distinct Ang-(1–7) receptor in the brain, the G-protein-coupled receptor Mas, encoded by the Mas protooncogene. We also show that the genetic deletion of this receptor abolishes the Ang-(1–7)-induced enhancement of LTP. Thus, we firstly demonstrate that Ang-(1–7) influences the induction of LTP in limbic structures implicating its distinct function in learning and memory mechanisms; secondly, we have identified Mas as a functional receptor for Ang-(1–7) in the brain.