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Subcellular distribution of cGMP signalling proteins in VSMCs of IRAG KO mice

Stimulation of cGMP signalling cascade in smooth muscle results in decreased intracellular Ca2+ levels and thus muscle relaxation. Inositoltrisphosphate Receptor 1 (IP3R1) – a Ca2+ release channel located in the membrane of sarcoplasmatic reticulum (SR) – is inhibited by the phosphorylation of IP3R1 associated cGMP kinase dependent substrate (IRAG) via cGMPkinase1β (cGK1β). On the other hand, Ca2+ is pumped back into SR by the Sarco/Endoplasmatic Reticulum Ca2+ ATPase (SERCA), which is inhibited by Phospholamban (PLB). Phosphorylation of PLB by cGK1 suppresses its inhibitory effect on SERCA. To characterize the subcellular distribution of these cGMP signalling proteins upon deletion of IRAG, aortic vascular smooth muscle cells (VSMCs) of IRAG KO mice were immunohistochemically analyzed and compared to VSMCs of littermate wild type animals. Furthermore we investigated the effects of treatment with 8Br-cGMP on the distribution of these proteins in IRAG KO VSMCs versus WT VSMCs.

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Correspondence to Bernhard Hieke.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Hieke, B., Schlossmann, J. Subcellular distribution of cGMP signalling proteins in VSMCs of IRAG KO mice. BMC Pharmacol 9 (Suppl 1), P25 (2009).

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