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  • Open Access

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

BMC Pharmacology20099(Suppl 1):P25

Published: 11 August 2009


  • Smooth Muscle
  • Muscle Cell
  • Smooth Muscle Cell
  • Signalling Cascade
  • Vascular Smooth Muscle

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.

Authors’ Affiliations

Lehrstuhl für Pharmakologie und Toxikologie, Universität Regensburg, Germany


© Hieke and Schlossmann; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.