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

K Hellner; T Walther; M Schubert; D Albrecht

doi:10.1016/j.mcn.2005.03.012

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

Mol Cell Neurosci. 2005 Jul;29(3):427-35. doi: 10.1016/j.mcn.2005.03.012.

Authors

K Hellner¹, T Walther, M Schubert, D Albrecht

Affiliation

¹ Institute of Neurophysiology (Charité, CCM), Humboldt University Berlin, Tucholskystr. 2, D-10117 Berlin, Germany.

PMID: 15950155
DOI: 10.1016/j.mcn.2005.03.012

Abstract

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.

MeSH terms

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 Mas
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

Substances

Angiotensin II Type 1 Receptor Blockers
Enzyme Inhibitors
Peptide Fragments
Proto-Oncogene Mas
Proto-Oncogene Proteins
Receptor, Angiotensin, Type 1
Receptors, G-Protein-Coupled
Angiotensin I
angiotensin I (1-7)