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Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract
  1. L E Sander1,
  2. A Lorentz2,
  3. G Sellge3,
  4. M Coëffier5,
  5. M Neipp6,
  6. T Veres7,
  7. T Frieling8,
  8. P N Meier4,
  9. M P Manns4,
  10. S C Bischoff9
  1. 1Medical School of Hannover, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover, Germany, and University Hospital (UKA), of Aachen University (RWTH), Department of Internal Medicine III, Aachen, Germany
  2. 2University of Hohenheim, Department of Nutritional Medicine and Prevention, Stuttgaet, Germany
  3. 3Medical School of Hannover, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover, Germany, and Inserm U389, Institut Pasteur, Paris, France
  4. 4Medical School of Hannover, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover, Germany
  5. 5Medical School of Hannover, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany, and Appareil Digestif Environnement et Nutrition (ADEN EA 3234, IFR 23), Rouen, France
  6. 6Medical School of Hannover, Department of Visceral and Transplant Surgery, Hannover, Germany
  7. 7Fraunhofer Institute of Toxicology and Experimental Medicine, Department of Allergy and Immunology, Hannover, Germany
  8. 8Medical Centre Krefeld, Department of Gastroenterology, Hepatology, and Neurogastroenterology, Krefeld, Germany
  9. 9University of Hohenheim, Department of Nutritional Medicine and Prevention, Stuttgart, Germany
  1. Correspondence to:
    Professor S C Bischoff
    Department of Nutritional Medicine and Prevention (140b), University of Hohenheim, D-70593 Stuttgart, Germany; bischoff.stephan{at}uni-hohenheim.de

Abstract

Background and aims: Histamine is known as a regulator of gastrointestinal functions, such as gastric acid production, intestinal motility, and mucosal ion secretion. Most of this knowledge has been obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the human gastrointestinal tract are unclear.

Methods: We analysed HR expression in human gastrointestinal tissue specimens by quantitative reverse transcription-polymerase chain reaction and immunostaining.

Results: We found that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in the distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, and rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent in the human enteric nervous system; however, H1R and H2R were found on ganglion cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the muscular layers of human intestine stained positive for both H1R and H2R. Immune cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of endoscopic biopsies from patients with food allergy and irritable bowel syndrome revealed significantly elevated H1R and H2R mRNA levels compared with controls.

Conclusions: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases.

  • ENS, enteric nervous system
  • FA, food allergy
  • FB, fibroblasts
  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • HNS, horse native serum
  • HR, histamine receptor
  • IBS, irritable bowel syndrome
  • LPMC, lamina propria mononuclear cells
  • MC, mast cells
  • PBMC, peripheral blood mononuclear cells
  • PGP, protein gene product
  • RT-PCR, reverse transcription-polymerase chain reaction
  • SDS, sodium dodecyl sulphate
  • histamine
  • intestine
  • irritable bowel syndrome
  • inflammatory bowel disease
  • food allergy

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Footnotes

  • Published online first 18 November 2005

  • Conflict of interest: None declared.

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