Volume 11 Supplement 1

5th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access

Interaction between bradykinin and urodilatin - a possible mechanism of clinical relevance

  • Marina Dobrivojević1Email author,
  • Aleksandra Sinđić1,
  • Bojana Nikitović1,
  • Bayram Edemir2,
  • Eberhard Schlatter2,
  • Wolf-Georg Forssmann3 and
  • Jochen R Hirsch3
BMC Pharmacology201111(Suppl 1):P21

https://doi.org/10.1186/1471-2210-11-S1-P21

Published: 1 August 2011

Background

Bradykinin (BK) plays a significant role in pathophysiology of different diseases from angioedema to brain stroke and heart attack by inducing vasodilatation and increasing capillary permeability. We investigate the potential effects of natriuretic peptides on BK signaling by measuring membrane potential (Vm) of HEK293 cells using the whole cell patch clamp technique. HEK293-cells are an excellent model since they display the natriuretic peptide receptor type A as well as both BK receptors (BR1 and BR2).

Results

Starting Vm was -53.5 ± 1.1 mV, n = 184. To detect viability of the cells hyperkalemic conditions were used (changing K+ from 3.6 mM to 18.6 mM) which depolarized HEK293 cells by 9.7 ± 0.4 mV, n = 182. BK (100 nM) depolarized HEK293 cells by ΔVm = 3.0 ± 0.2 mV, n=57 (figure 1). Our preliminary results show that the BK induced depolarization by activating bradykinin receptor type 2 (BR2) and further down the signaling pathway activation of Ca2+-dependent Cl- channels (Figure 1).
Figure 1

Effects of natriuretic peptides and cGMP signaling pathway on bradykinin (BK) action. BK – bradykinin; NPPB – inhibitor of Ca2+-dependent Cl- channels; ANP – atrial natriuretic peptide; URO – urodilatin; BNP – brain natriuretic peptide; CNP – C-type natiuretic peptide; KT5823 – inhibitor protein kinase G. Number of experiments are given in brackets. * p<0.05 compared to depolarizations caused by bradykinin alone

Natriuretic peptides display different effects on the BK-induced depolarization due to activation of Ca2+-dependent Cl--channels. While ANP, urodilatin, BNP (all acting though guanylate cyclase A) and 8-Br cGMP inhibited the BK-induced depolarization, CNP (acting through guanylate cyclase B) failed to do so (Figure 1). Effects of urodilatin on BK-induced deoplarization could be reversed by inhibiting protein kinase G (using the specific inhibitor KT5823) suggesting an inhibitory role of natriuretic peptides via GC-A, cGMP and PKG in BK signaling.

Conclusion

From our results we could speculate that natriuretic peptides might display beneficial effects in different pathological conditions caused by BK.

Declarations

Acknowledgements

These materials are based on work financed by the National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia and the CardioPep Pharma GmbH, Germany.

Authors’ Affiliations

(1)
Dept. Physiology, School of Medicine, Croatian Institute for Brain Research, University of Zagreb
(2)
Universitätsklinikum Münster, Experimentelle Nephrologie
(3)
Cardiopep Pharma GmbH

Copyright

© Dobrivojevićć et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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