Letter | Published:

AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration

Nature volume 407, pages 9498 (07 September 2000) | Download Citation

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Abstract

The vasopressor angiotensin II regulates vascular contractility and blood pressure through binding to type 1 angiotensin II receptors (AT1; refs 1, 2). Bradykinin, a vasodepressor, is a functional antagonist of angiotensin II (ref. 3). The two hormone systems are interconnected by the angiotensin-converting enzyme, which releases angiotensin II from its precursor and inactivates the vasodepressor bradykinin4. Here we show that the AT 1 receptor and the bradykinin (B2) receptor also communicate directly with each other. They form stable heterodimers, causing increased activation of Gαq and Gαi proteins, the two major signalling proteins triggered by AT1. Furthermore, the endocytotic pathway of both receptors changed with heterodimerization. This is the first example of signal enhancement triggered by heterodimerization of two different vasoactive hormone receptors.

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Acknowledgements

We thank B. Nürnberg, for anti-Gα-common antibodies, and J. Heukeshoven for helpful advice on high-resolution electrophoresis of hydrophobic proteins. This work was supported in part by the Deutsche Forschungsgemeinschaft.

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Affiliations

  1. *Genetics Engineering and Biotechnology Research Institute, Manchiat El-Olama, El-Dekheela , Alexandria, Egypt

    • Said AbdAlla
  2. †Heinrich Pette Institut, Martinistraβe 52, 20251 Hamburg, Germany

    • Heinz Lother
  3. ‡Institut für Pharmakologie, Versbacher Straβe 9, 97078 Würzburg, Germany

    • Ursula Quitterer

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Correspondence to Ursula Quitterer.

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https://doi.org/10.1038/35024095

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