Skip to main content
SpringerLink
Log in

Immunohistochemical localization of the angiotensin-(1–7) receptor Mas in the murine forebrain

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Apart from the well-known biologically active angiotensin II, other biologically active angiotensins have been discovered, including angiotensin IV and angiotensin-(1–7). Some years ago, we and others discovered that the Mas proto-oncogene encodes a receptor that is essential for angiotensin-(1–7) signaling. Angiotensin-(1–7) is not only expressed in the periphery but also within the brain. Based on that, we examined the distribution of Mas within the murine brain, using an antibody directed against the 3rd cytoplasmic loop of the receptor protein. Strongest Mas protein expression was detected in the dentate gyrus of the hippocampus and within the piriform cortex. However, Mas protein expression is not restricted to these areas, since Mas immunopositive neurons were also seen in different parts of the cortex, hippocampus, amygdala, basal ganglia, thalamus and hypothalamus. Based on the expression of Mas protein in the cortex and the limbic system, angiotensin-(1–7) signaling may play a role in synaptic plasticity, learning, memory and emotion, as has been described for angiotensin II and IV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Albrecht D (2007) Angiotensin-(1–7)-induced plasticity changes in the lateral amygdala are mediated by COX-2 and NO. Learn Mem 14:177–184

    Article  PubMed  CAS  Google Scholar 

  • Alenina N, Xu P, Rentzsch B, Patkin EL, Bader M (2008) Genetically altered animal models for Mas and angiotensin-(1–7). Exp Physiol 93:528–537

    Article  PubMed  CAS  Google Scholar 

  • Becker LK, Etelvino GM, Walther T, Santos RA, Campagnole-Santos MJ (2007) Immunofluorescence localization of the receptor Mas in cardiovascular-related areas of the rat brain. Am J Physiol Heart Circ Physiol 293:H1416–H1424

    Article  PubMed  CAS  Google Scholar 

  • Block CH, Santos RA, Brosnihan KB, Ferrario CM (1988) Immunocytochemical localization of angiotensin-(1–7) in the rat forebrain. Peptides 9:1395–1401

    Article  PubMed  CAS  Google Scholar 

  • Brown K (1989) Angiotensin receptors are implicated in the mechanism of mas action. TIPS 10:87–89

    PubMed  CAS  Google Scholar 

  • Bunnemann B, Fuxe K, Metzger R, Mullins J, Jackson TR, Hanley MR, Ganten D (1990) Autoradiographic localization of mas-proto-oncogene mRNA in adult rat brain using in situ hybridization. Neurosci Lett 114:147–153

    Article  PubMed  CAS  Google Scholar 

  • Castro CH, Santos RA, Ferreira AJ, Bader M, Alenina N, Almeida AP (2005) Evidence for a functional interaction of the angiotensin-(1–7) receptor Mas with AT1 and AT2 receptors in the mouse heart. Hypertension 46:937–942

    Article  PubMed  Google Scholar 

  • Chappell MC, Brosnihan KB, Diz DI, Ferrario CM (1989) Identification of angiotensin-(1–7) in rat brain. Evidence for differential processing of angiotensin peptides. J Biol Chem 264:16518–16523

    PubMed  CAS  Google Scholar 

  • Ferrario CM, Barnes KL, Block CH, Brosnihan KB, Diz DI, Khosla MC, Santos RA (1990) Pathways of angiotensin formation and function in the brain. Hypertension 15:I13–I19

    PubMed  CAS  Google Scholar 

  • Franklin KBJ, Paxinos G (2008) The mouse brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  • Freeman EJ, Chisolm GM, Ferrario CM, Tallant EA (1996) Angiotensin-(1–7) inhibits vascular smooth muscle cell growth. Hypertension 28:104–108

    PubMed  CAS  Google Scholar 

  • Gwathmey TM, Westwood BM, Pirro NT, Tang L, Rose JC, Diz DI, Chappell MC (2010) Nuclear angiotensin-(1–7) receptor is functionally coupled to the formation of nitric oxide. Am J Physiol Renal Physiol 299:F983–F990

    Article  PubMed  CAS  Google Scholar 

  • Hellner K, Walther T, Schubert M, Albrecht D (2005) Angiotensin-(1–7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas. Mol Cell Neurosci 29:427–435

    Article  PubMed  CAS  Google Scholar 

  • Jackson TR, Blair LAC, Marshall J, Goedert M, Hanley MR (1988) The mas oncogene encodes an angiotensin receptor. Nature 335:437–440

    Article  PubMed  CAS  Google Scholar 

  • Jung MW, Larson J (1994) Further characteristics of long-term potentiation in piriform cortex. Synapse 18:298–306

    Article  PubMed  CAS  Google Scholar 

  • Kostenis E, Milligan G, Christopoulos A, Sanchez-Ferrer CF, Heringer-Walther S, Sexton PM, Gembardt F, Kellett E, Martini L, Vanderheyden P, Schultheiss HP, Walther T (2005) G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor. Circulation 111:1806–1813

    Article  PubMed  CAS  Google Scholar 

  • Kumar M, Grammas P, Giacomelli F, Wiener J (1996) Selective expression of c-mas proto-oncogene in rat cerebral endothelial cells. NeuroReport 8:93–96

    Article  PubMed  CAS  Google Scholar 

  • Martin KA, Grant SG, Hockfield S (1992) The mas proto-oncogene is developmentally regulated in the rat central nervous system. Brain Res Dev Brain Res 68:75–82

    Article  PubMed  CAS  Google Scholar 

  • Metzger R, Bader M, Ludwig G, Berberich C, Bunnemann B, Ganten D (1995) Expression of the mouse and rat mas proto-oncogene in the brain and peripheral tissue. FEBS 357:27–32

    Article  CAS  Google Scholar 

  • Peiro C, Vallejo S, Gembardt F, Azcutia V, Heringer-Walther S, Rodriguez-Manas L, Schultheiss HP, Sanchez-Ferrer CF, Walther T (2007) Endothelial dysfunction through genetic deletion or inhibition of the G protein-coupled receptor Mas: a new target to improve endothelial function. J Hypertens 25:2421–2425

    Article  PubMed  CAS  Google Scholar 

  • Pekcec A, Loscher W, Potschka H (2006) Neurogenesis in the adult rat piriform cortex. NeuroReport 17:571–574

    Article  PubMed  Google Scholar 

  • Rivers LE, Young KM, Rizzi M, Jamen F, Psachoulia K, Wade A, Kessaris N, Richardson WD (2008) PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 11:1392–1401

    Article  PubMed  CAS  Google Scholar 

  • Sampaio WO, Nascimento AA, Santos RA (2003) Systemic and regional hemodynamic effects of angiotensin-(1–7) in rats. Am J Physiol Heart Circ Physiol 284:H1985–H1994

    PubMed  CAS  Google Scholar 

  • Santos RA, Campagnole-Santos MJ (1994) Central and peripheral actions of angiotensin-(1–7). Braz J Med Biol Res 27:1033–1047

    PubMed  CAS  Google Scholar 

  • Santos RA, Campagnole-Santos MJ, Baracho NC, Fontes MA, Silva LC, Neves LA, Oliveira DR, Caligiorne SM, Rodrigues AR, Gropen JC (1994) Characterization of a new angiotensin antagonist selective for angiotensin-(1–7): evidence that the actions of angiotensin-(1–7) are mediated by specific angiotensin receptors. Brain Res Bull 35:293–298

    Article  PubMed  CAS  Google Scholar 

  • Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T (2003) Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A 100:8258–8263

    Article  PubMed  CAS  Google Scholar 

  • Tallant EA, Ferrario CM, Gallagher PE (2005) Angiotensin-(1–7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol Heart Circ Physiol 289:H1560–H1566

    Article  PubMed  CAS  Google Scholar 

  • Tesanovic S, Vinh A, Gaspari TA, Casley D, Widdop RE (2010) Vasoprotective and atheroprotective effects of angiotensin (1–7) in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 30:1606–1613

    Article  PubMed  CAS  Google Scholar 

  • von Bohlen und Halbach O (2005) The renin-angiotensin system in the mammalian central nervous system. Curr Protein Pept Sci 6:355–371

    Article  PubMed  CAS  Google Scholar 

  • von Bohlen und Halbach O (2011) Immunohistological markers for proliferative events, gliogenesis, and neurogenesis within the adult hippocampus. Cell Tissue Res 345:1–19

    Article  PubMed  CAS  Google Scholar 

  • von Bohlen und Halbach O, Walther T, Bader M, Albrecht D (2000) Interaction between Mas and the angiotensin AT1 receptor in the amygdala. J Neurophysiol 83:2012–2021

    PubMed  CAS  Google Scholar 

  • von Bohlen und Halbach O, Hinz U, Unsicker K, Egorov AV (2005) Distribution of TRPC1 and TRPC5 in medial temporal lobe structures of mice. Cell Tissue Res 322:201–206

    Article  PubMed  Google Scholar 

  • Walther T, Balschun D, Voigt J-P, Fink H, Zuschratter W, Birchmeier C, Ganten D, Bader M (1998) Sustained long-term potentiation and anxiety in mice lacking the Mas protooncogene. J Biol Chem 273:11867–11873

    Article  PubMed  CAS  Google Scholar 

  • Young D, Waitches G, Birchmeier C, Fasano O, Wigler M (1986) Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell 45:711–719

    Article  PubMed  CAS  Google Scholar 

  • Zhu XJ, Hua Y, Jiang J, Zhou QG, Luo CX, Han X, Lu YM, Zhu DY (2006) Neuronal nitric oxide synthase-derived nitric oxide inhibits neurogenesis in the adult dentate gyrus by down-regulating cyclic AMP response element binding protein phosphorylation. Neuroscience 141:827–836

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The study was supported by a grant from the “Forschungsverbund Neurowissenschaften Greifswald”. We wish to thank Mrs. Hanisch for excellent technical assistance.

Author information

Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, Universitätsmedizin Greifswald, Ernst Moritz Arndt University of Greifswald, Friedrich-Löffler-Straße-23c, 17487, Greifswald, Germany

    M. Freund & O. von Bohlen und Halbach

  2. Centre Cardiovascular and Metabolic Research (CCMR), Hull York Medical School, University of Hull, Hull, HU6 7RX, UK

    T. Walther

Authors
  1. M. Freund
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Walther
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. von Bohlen und Halbach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. von Bohlen und Halbach.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Freund, M., Walther, T. & von Bohlen und Halbach, O. Immunohistochemical localization of the angiotensin-(1–7) receptor Mas in the murine forebrain. Cell Tissue Res 348, 29–35 (2012). https://doi.org/10.1007/s00441-012-1354-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-012-1354-3

Keywords

Search

Navigation