Angiotensin-(1-7) through Mas receptor up-regulates neuronal norepinephrine transporter via Akt and Erk1/2-dependent pathways

J. Neurochem. (2012) 120, 46–55. As angiotensin (Ang) (1–7) decreases norepinephrine (NE) content in the synaptic cleft, we investigated the effect of Ang‐(1–7) on NE neuronal uptake in spontaneously hypertensive rats. [3H]‐NE neuronal uptake was measured in isolated hypothalami. NE transporter (NET...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neurochemistry 2012-01, Vol.120 (1), p.46-55
Main Authors: Lopez Verrilli, María A., Rodriguez Fermepín, Martín, Longo Carbajosa, Nadia, Landa, Silvina, Cerrato, Bruno D., García, Silvia, Fernandez, Belisario E., Gironacci, Mariela M.
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Acute effects
AKT protein
Angiotensin
Angiotensin I - pharmacology
angiotensin-(1-7)
Animals
Antibodies
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Blood pressure
Blotting, Western
Cardiology. Vascular system
Cell receptors
Cell structures and functions
Cells, Cultured
Cycloheximide
Extracellular signal-regulated kinase
Fundamental and applied biological sciences. Psychology
Homeostasis
Hypertension
Hypothalamus
Kinases
Long-term effects
Mas receptor
Medical sciences
Mitogen-Activated Protein Kinase 1 - physiology
Mitogen-Activated Protein Kinase 3 - physiology
Molecular and cellular biology
Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)
mRNA
Neurochemistry
Neurons
Neurons - metabolism
Norepinephrine
Norepinephrine Plasma Membrane Transport Proteins - biosynthesis
Norepinephrine transporter
norepinephrine uptake
Oncogene Protein v-akt - physiology
Peptide Fragments - pharmacology
Proto-Oncogene Proteins - drug effects
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Receptor mechanisms
Receptors, G-Protein-Coupled - drug effects
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Signal Transduction - drug effects
Synaptic cleft
Up-Regulation - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:J. Neurochem. (2012) 120, 46–55. As angiotensin (Ang) (1–7) decreases norepinephrine (NE) content in the synaptic cleft, we investigated the effect of Ang‐(1–7) on NE neuronal uptake in spontaneously hypertensive rats. [3H]‐NE neuronal uptake was measured in isolated hypothalami. NE transporter (NET) expression was evaluated in hypothalamic neuronal cultures by western‐blot. Ang‐(1–7) lacked an acute effect on neuronal NE uptake. Conversely, Ang‐(1–7) caused an increase in NET expression after 3 h incubation (40 ± 7%), which was blocked by the Mas receptor antagonist, a PI3‐kinase inhibitor or a MEK1/2 inhibitor suggesting the involvement of Mas receptor and the PI3‐kinase/Akt and MEK1/2‐ERK1/2 pathways in the Ang‐(1–7)‐stimulated NET expression. Ang‐(1–7) through Mas receptors stimulated Akt and ERK1/2 activities in spontaneously hypertensive rat neurons. Cycloheximide attenuated Ang‐(1–7) stimulation of NET expression suggesting that Ang‐(1–7) stimulates NET synthesis. In fact, Ang‐(1–7) increased NET mRNA levels. Thus, we evaluated the long‐term effect of Ang‐(1–7) on neuronal NE uptake after 3 h incubation. Under this condition, Ang‐(1–7) increased neuronal NE uptake by 60 ± 14% which was blocked by cycloheximide and the Mas receptor antagonist. Neuronal NE uptake and NET expression were decreased after 3 h incubation with an anti‐Ang‐(1–7) antibody. Ang‐(1–7) induces a chronic stimulatory effect on NET expression. In this way, Ang‐(1–7) may regulate a pre‐synaptic mechanism in maintaining appropriate synaptic NE levels during hypertensive conditions. Central NET upregulation by angiotensin‐(1‐7) in hypertension As angiotensin (Ang) (1–7) decreases norepinephrine (NE) content in the synaptic cleft, we investigated the effect of Ang‐(1–7) on centrally NE neuronal uptake, the main mechanism for NE removal from the synaptic cleft, in hypothalamic neurons from hypertensive rats. We showed that Ang‐(1–7) causes a long‐term stimulatory effect on NE neuronal uptake by increasing NE transporter expression. This effect is coupled to Mas receptor activation acting through both MEK1/2‐ERK1/2 and PI3‐kinase/Akt‐dependent pathways. In this way, Ang‐(1–7) may regulate a pre‐synaptic mechanism in maintaining appropriate synaptic NE levels during hypertensive conditions, thus contributing to the modulation of NE homeostasis and blood pressure regulation.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2011.07552.x