Volume 9 Supplement 1

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

Open Access

The role of cGMP-cGKI-signaling for duodenal bicarbonate secretion

  • Beate Spiessberger1Email author,
  • Pascal Weinmeister1,
  • Franz Hofmann1,
  • Claudia Werner1,
  • Dieter Saur2,
  • Ursula Seidler3,
  • Wen Zheng3,
  • Jens Schlossmann4 and
  • Robert Lukowski1, 5
BMC Pharmacology20099(Suppl 1):P67

https://doi.org/10.1186/1471-2210-9-S1-P67

Published: 11 August 2009

Background

The duodenal mucosa protects itself from gastric acid injury by the secretion of bicarbonate from epithelial cells. We determined a possible role of the cGMP-cGKI pathway for the duodenal bicarbonate secretion by studying conventional cGKI knockouts (cGKI-KOs) and rescue mice (RM) that express either the cGKIα or Iβ isoform in SM22α positive smooth muscle cells [1].

Results

The basal secretion rate of bicarbonate was strongly reduced in the different gene-targeted cGKI mice. Moreover, the H+ induced bicarbonate secretion was significantly increased in controls but nearly absent in all cGKI mutants, whereas invasive pH measurements in fasted animals demonstrated that the gastric acid production of all genotypes was similar. The dysfunction of the duodenal bicarbonate secretion of RM and cGKI-KO animals was associated with severe gastrointestinal bleedings, which were caused by the age-dependent aggravation of an epithelial ulceration that localized to the papilla Vateri.

Conclusion

The analysis of cGKI-KO and RM indicates that a cGMP-cGKI-dependent pathway is present in non-smooth muscle cells of the duodenum that is involved in the basal and acid-induced secretion of bicarbonate. The inability to secrete adequate amounts of bicarbonate ultimately leads to duodenal ulceration. We postulate that the continuous blood loss accounts for the chronic anemia of cGKI mutant mice and causes the premature death of the cGKI-KOs and RM.

Declarations

Acknowledgements

We greatly thank Teodora Ruttner for her skilled technical support.

Authors’ Affiliations

(1)
For 923 at Institut für Pharmakologie und Toxikologie, TU München
(2)
Department of Internal Medicine II, Klinikum Rechts der Isar, TU München
(3)
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School
(4)
Department of Pharmacology and Toxicology, Universität Regensburg
(5)
Institut für Pharmakologie und Toxikologie, TU München

References

  1. Weber S, Bernhard D, Lukowski R, Weinmeister P, Wörner R, Wegener JW, Valtcheva N, Feil S, Schlossmann J, Hofmann F, Feil R: Rescue of cGMP kinase I knockout mice by smooth muscle specific expression of either isozyme. Circ Res. 2007, 101: 1096-103. 10.1161/CIRCRESAHA.107.154351.View ArticlePubMedGoogle Scholar

Copyright

© Spiessberger et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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