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Genetic dissection of the signaling pathways that control gastric acid secretion

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Abstract

Gastric acid secretion is regulated by endocrine, paracrine and neurocrine signals via at least three pathways, the gastrin-histamine pathway, the CCK-somatostatin pathway and the neural pathway. Genetically-engineered mice, subjected to targeted gene disruption (i.e., knockout mice), have been used to dissect the signaling pathways that are responsible for the complexity of the regulation of acid secretion in vivo. Both gastrin knockout and gastrin/CCK2 receptor knockout mice displayed greatly impaired acid secretion, presumably because of the loss of the gastrin-histamine pathway. Gastrin/CCK double-knockout mice had a relatively high percentage of active parietal cells with a maintained ability to respond with copious acid secretion to pylorus ligation-evoked vagal stimulation and to a histamine challenge. The low acid secretion in gastrin knockout mice and gastrin/CCK2 receptor knockout mice and the restoration of acid secretion in gastrin/CCK double-knockout mice suggest that CCK plays an important role as inhibitor of the parietal cells via the CCK-somatostatin pathway by stimulating the CCK1 receptor of the D cell. In the absence of both the gastrin-histamine and the CCK-somatostatin pathway (as in gastrin/CCK2 receptor double-knockout mice), the control of acid secretion is probably taken over by neural pathways, explaining the high acid output. The observations illustrate the complexity and plasticity of the acid regulatory mechanisms. It seems that one pathway may be suppressed or allowed to dominate over the others depending on the circumstances.

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Authors and Affiliations

  1. Department of Surgery, University Hospital Trondheim, Olav Kyrres gate 17, 7006, Trondheim, Norway

    Duan Chen

  2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    Duan Chen & Chun-Mei Zhao

  3. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

    Lennart Friis-Hansen

  4. Department of Pharmacology, University of Lund, Lund, Sweden

    Rolf Håkanson

Authors
  1. Duan Chen
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  2. Lennart Friis-Hansen
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  3. Rolf Håkanson
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  4. Chun-Mei Zhao
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Correspondence to Duan Chen.

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Chen, D., Friis-Hansen, L., Håkanson, R. et al. Genetic dissection of the signaling pathways that control gastric acid secretion. Inflammopharmacol 13, 201–207 (2005). https://doi.org/10.1163/156856005774423872

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  • DOI: https://doi.org/10.1163/156856005774423872

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