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Volume 9 Supplement 1

4th International Conference of cGMP Generators, Effectors and Therapeutic Implications

Cardiovascular and gastrointestinal function of IRAG

BMC Pharmacology volume 9, Article number: P11 (2009) Cite this article

Background

Signalling by NO/cGMP is very important for regulation of vascular tone and gastrointestinal motility. One important signalling pathway of cGMP-dependent protein kinase type I (cGKI) is mediated by IRAG (I P3 R eceptor A ssociated cG KI substrate) which is highly expressed in smooth muscle of cardiovascular and gastrointestinal tissue. In order to elucidate the physiological role of IRAG we generated IRAG knockout mice by targeted deletion of exon 3. These mice show an enlarged gastrointestinal tract including pylorus stenosis.

Results

Exogenous and endogenous NO and cGMP stimulation relaxes hormone induced contraction of wild type aortic vessels as well as gastrointestinal tissues of colon and jejunum. This effect is significantly reduced in IRAG – deficient animals. Furthermore, activation of particular guanylyl cyclase by atrial natriuretic peptide (ANP) shows a reduced relaxing effect in IRAG knockout tissue strips. The expression levels of other cGKI substrates and the NO-induced cGMP synthesis are not affected in these tissues from IRAG KO mice.

Conclusion

These results indicate that IRAG signalling is essentiaI for smooth muscle relaxation by NO/cGMP and ANP/cGMP.

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Authors and Affiliations

  1. Lehrstuhl für Pharmakologie & Toxikologie, Universität Regensburg, Germany

    Matthias Desch & Jens Schlossmann

  2. Institut für Pharmakologie & Toxikologie, Technische Universität München, Germany

    Jörg Wegener & Franz Hofmann

  3. Interfakultäres Institut für Biochemie, Universität Tübingen, Germany

    Robert Feil & Susi Feil

  4. Urologische Klinik & Poliklinik, Klinikum Großhadern, LMU München, Germany

    Katja Sigl

Authors
  1. Matthias Desch
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  2. Katja Sigl
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  3. Jörg Wegener
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  4. Robert Feil
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  5. Susi Feil
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  6. Franz Hofmann
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  7. Jens Schlossmann
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Corresponding author

Correspondence to Matthias Desch.

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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 (https://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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Desch, M., Sigl, K., Wegener, J. et al. Cardiovascular and gastrointestinal function of IRAG. BMC Pharmacol 9 (Suppl 1), P11 (2009). https://doi.org/10.1186/1471-2210-9-S1-P11

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  • DOI: https://doi.org/10.1186/1471-2210-9-S1-P11

Keywords

  • Atrial Natriuretic Peptide
  • Guanylyl Cyclase
  • Smooth Muscle Relaxation
  • Deficient Animal
  • IRAG Signalling

BMC Pharmacology

ISSN: 1471-2210