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Open Access

Function of IRAG and the phosphorylation of the InsP3R-I for the NO/cGMP-dependent inhibition of platelet aggregation

BMC Pharmacology201111(Suppl 1):P58

https://doi.org/10.1186/1471-2210-11-S1-P58

Published: 1 August 2011

Background

Precondition for activation and aggregation of platelets is a rise in intracellular calcium concentration which can be inhibited by activation of the NO/cGMP/cGKI signalling cascade. The cGMP-dependent Kinase I (cGKI) is assembled in a macrocomplex with the Inositoltrisphosphate receptor I (InsP3R-I) and the Inositoltrisphosphate receptor associated cGMP kinase substrate (IRAG).

Results

We investigated the relevance of IRAG and the cGKI stimulated phosphorylation of the calcium channel InsP3R-I for the NO/cGMP-dependent inhibition of platelet aggregation and adhesion.

After incubation with different agonists (collagen, thrombin, TxA2) we performed aggregation experiments with platelets of WT and IRAG-KO mice, thereby the IRAG-KO platelets aggregated stronger than the WT platelets. After preincubation with NO/cGMP the inhibition of aggregation was decreased in IRAG-KO platelets compared to WT platelets. Furthermore, GPIIb/IIIa-mediated adhesion of platelets to fibrinogen could only weakly be inhibited in IRAG-deficient platelets contrary to WT platelets. The cGKI-mediated stimulation of InsP3R-I phosphorylation showed an equal increase in WT and IRAG-KO platelets.

Conclusion

These results revealed that IRAG plays an important role in the NO/cGMP-dependent inhibition of platelet aggregation. However, the cGMP-stimulated phosphorylation of InsP3R-I is not necessary for the inhibition of platelet aggregation.

Authors’ Affiliations

(1)
Department of Pharmacology and Toxicology, University of Regensburg

Copyright

© Salb 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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