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Histamine-2 Receptor Antagonist in the Treatment of Gastroesophageal Reflux Disease

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Esophageal and Gastric Disorders in Infancy and Childhood

Abstract

In the stomach, gastric acid is secreted by the parietal cell. Several factors such as the presence of food, the smell, and/or taste of food and stress have influence on gastric acid secretion. Gastrin, histamine, acetylcholine, and prostaglandin regulate gastric acid secretion through the gastrin, the histamine, the muscarine, and the prostaglandin receptors, respectively (Fig. 88.1). In contrast, the prostaglandin receptor downregulates the gastric acid secretion and protects against the erosive irritation of gastric acid. The presence of food raises the pH in the stomach, which stimulates gastrin cells in the antrum of the stomach to produce gastrin. Subsequently, gastrin is then excreted into the bloodstream and stimulates the receptors at the parietal cell (the direct pathway) as well as the receptors at the adjacent endocrine cell (the histamine pathway). Acetylcholine (neurotransmitter) has a similar working mechanism and demonstrates the neural influence on gastric acid secretion. Histamine is produced by the endocrine cells and stimulates the histamine-2 receptor at the adjacent parietal cells. This stimulation results in an increase of intracellular cAMP, which in turn activates the H+/K+-ATPase. Also at the parietal cell, the acetylcholine binds and activates the acetylcholine receptor, which results in the opening of calcium channels. This leads to a calcium influx. In addition, gastrin binds and activates the gastrin receptors, which results in the mobilization of the intracellular calcium pool. These two additional mechanisms help the cAMP to activate the H+/K+-ATPase. This process will actively shift H+-ions into the lumen of the stomach in exchange to K+-ions (Fig. 88.1). The histamine, gastrin, acetylcholine, and prostaglandin receptors together form a mechanism to balance the gastric acid production for the digestion of food and the downregulation for the protection of the esophagus, stomach, and duodenum.

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Author information

Authors and Affiliations

  1. Department of Pediatric Gastroenterology and Nutrition, Emma Children’s Hospital/Amsterdam Medical Centre Amsterdam, Amsterdam, The Netherlands

    Herbert M. van Wering MD, PhD & Marc A. Benninga MD, PhD

  2. Department of Pediatrics, Amsterdam Medical Centre, Room G8-205, 22660, Amsterdam, 1100 DD, The Netherlands

    Marc A. Benninga MD, PhD

Authors
  1. Herbert M. van Wering MD, PhD
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  2. Marc A. Benninga MD, PhD
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Corresponding author

Correspondence to Marc A. Benninga MD, PhD .

Editor information

Editors and Affiliations

  1. Medical University of Graz, Graz, Austria

    Holger Till

  2. Sheffield Children’s Hospital, Paediatric Gastroenterology Centre, Sheffield, United Kingdom

    Mike Thomson

  3. Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    John E. Foker

  4. Department Surgery, University of Missouri, Kansas City Children’s Mercy Hospital, Kansas City, Missouri, USA

    George W. Holcomb III

  5. University of Arizona, Tucson, Arizona, USA

    Khalid M. Khan

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van Wering, H.M., Benninga, M.A. (2017). Histamine-2 Receptor Antagonist in the Treatment of Gastroesophageal Reflux Disease. In: Till, H., Thomson, M., Foker, J., Holcomb III, G., Khan, K. (eds) Esophageal and Gastric Disorders in Infancy and Childhood. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11202-7_88

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  • DOI: https://doi.org/10.1007/978-3-642-11202-7_88

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