gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Effects of receptor heterodimerization on the angiotensin II stimulated AP-1 signaling

Effekte der Rezeptorheterodimerisierung auf die Angiotensin II stimulierte AP-1 Aktivierung

Meeting Abstract (Hypertonie 2004)

  • F. Gembardt - Charité Berlin - Campus Benjamin Franklin
  • A. Heiss - Charité Berlin - Campus Benjamin Franklin
  • J. Zhang - Erasmus Medical Center (Rotterdam, NL)
  • T. Walther - Erasmus Medical Center (Rotterdam, NL)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP41

The electronic version of this article is the complete one and can be found online at:

Published: August 10, 2005

© 2005 Gembardt et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



The renin angiotensin system (RAS) is well known for its important regulatory effects on blood pressure by interaction of its metabolite angiotensin (Ang) II with the AT1 receptor. It is also known that the RAS is involved in inflammatory processes like arteriosclerosis, since stimulation of the AT1 receptor leads to e.g. stimulation of transcription factors promoting inflammation. Recent investigations have postulated that heterodimerization with the AT2 or bradykinin receptor B2 influences the intracellular calcium signaling of the AT1 receptor and consequently altering blood pressure homeostasis. Thus we investigated the influence of the AT2 and the B2 receptor on the AngII-stimulated AT1-mediated activation of the transcription factor activator protein-1 (AP-1).

We examined the AP-1 activation with a dual luciferase assay in HEK293 cells transfected with plasmids containing the cDNA for the AT1, AT2, and/or B2 driven by a CMV promoter. For measurements cells were co-transfected with a plasmid coding for firefly-luciferase driven by an AP-1-activated promoter and a plasmid coding renilla-luciferase as an internal control.

None of the receptors influenced the AP-1-mediated luciferase production on basal conditions. However, stimulation with AngII (10-6M) in AT1-transfected cells mediated a 11.2-fold increase in luciferase production, whereas no increase could be observed in AT2- or B2-transfected cells. Importantly, co-transfection of AT1 with AT2 or B2 receptors led to a significant less pronounced increase in luciferase production (AT1/AT2: 4.8-fold; AT1/B2: 3.6-fold).

According to data from literature the AT2 receptor is also antagonizing the AT1-mediated AP-1 activation. Since our finding that the B2 receptor also antagonize AT1 signaling is conflicting recent publications, former conclusions of the impact of AT1/B2 heterodimerization in the etymology of preeclampsia has to be critically reasked.