Histamine Receptors: Vital Roles in Human Gastrointestinal Health

Estimated Read Time: Approximately 9 minutes

Keywords: Histamine Receptors, Histamine, Gastrointestinal, Receptors, H1R, H2R, IBS, H4R, H3R, Immune, Mucosa, Motility

Study Authors: ​​L. E. Sander, A. Lorentz, G. Sellge, M. Coe¨ffier, M. Neipp, T. Veres, T. Frieling, P. N. Meier, M. P. Manns, S. C. Bischoff

This article is a summary and written based on the study in the following link.  

Image illustrating the various histamine receptors (H1R, H2R, H4R) expressed in the human gastrointestinal tract.

Background and Aims

Histamine and histamine receptors plays a critical role in regulating gastrointestinal functions such as gastric acid production, intestinal motility, and mucosal ion secretion. While much of this understanding comes from animal studies, the expression and distribution of histamine receptors (HR) in the human gastrointestinal tract remain unclear. This study aimed to analyze the expression of HR in human gastrointestinal tissues using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunostaining.

Methods

  • HR Expression Analysis: HR expression was analyzed in human gastrointestinal tissue specimens using quantitative RT-PCR and immunostaining techniques.
  • Patient Samples: Thirty-three individuals undergoing bowel resection due to gastrointestinal cancer provided samples from unaffected tissue. Additionally, endoscopic biopsies from patients with irritable bowel syndrome (IBS) and food allergies (FA) were compared with controls.

Results

  • HR mRNA Expression: H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in HR distribution were found between different anatomical sites.
  • Immunostaining Results: H1R and H2R were present on ganglion cells of the myenteric plexus, epithelial cells, and intestinal fibroblasts. Immune cells expressed H1R, H2R, and low levels of H4R.
  • HR Expression in Gastrointestinal Disorders: Elevated levels of H1R and H2R mRNA were observed in patients with IBS and FA compared to controls, indicating altered HR expression in these conditions.

Discussion

Histamine modulates immune functions and is a significant mediator of gastrointestinal activities. This study reveals that H1R, H2R, and H4R are expressed in the human gastrointestinal tract, while H3R is not. The presence of HR in various cell types, including immune cells and fibroblasts, underscores histamine’s role in gastrointestinal physiology.

Implications for Gastrointestinal Disorders

The study’s findings suggest that HR expression patterns are altered in patients with IBS and FA, potentially contributing to the symptoms of these conditions. This supports the idea that targeting HR may be beneficial in managing gastrointestinal disorders characterized by altered secretion and motility.

Conclusion

This research provides the first comprehensive analysis of HR expression in the human gastrointestinal tract, highlighting the absence of H3R and the presence of H1R, H2R, and H4R. The elevated expression of H1R and H2R in IBS and FA patients suggests that histamine plays a crucial role in these conditions, paving the way for potential therapeutic interventions targeting HR.

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References

  • Barger G, Dale HH. Chemical structure and sympathomimetic actions of amines. J Physiol Pharmacol 1910;41:19–59.
  • Tanaka S, Hamada K, Yamada N, et al. Gastric acid secretion in L-histidine decarboxylase-deficient mice. Gastroenterology 2002;122:145–55.
  • Tari A, Yamamoto G, Sumii K, et al. Roles of histamine 2 receptor in increased expression of rat gastric H+-K+ ATPase-alpah-subunit induced by omeprazole. Am J Physiol 1993;265:G752–8.
  • Bennett A, Whitney B. A pharmacological study of the motility of the human gastrointestinal tract. Gut 1966;7:307–16.
  • Bertaccini G, Coruzzi G. An update on histamine H3 receptors and gastrointestinal functions. Dig Dis Sci 1995;40:2052–63.
  • Bolton TB, Clark JP, Kitamura K, et al. Evidence that histamine and carbachol may open the same ion channels in longitudinal smooth muscle of guinea-pig ileum. J Physiol 1981;320:363–79.
  • Harry J. The action of drugs on the circular muscle strip from guinea-pig isolated ileum. Br J Pharmacol 1963;20:399–417.
  • Kelly SJ, Stack WA, O’Donoghue DP, et al. Regulation of ion transport by histamine in human colon. Eur J Pharmacol 1995;12:203–9.
  • Wang YZ, Cooke HJ, Su HC, et al. Histamine augments colonic secretion in guinea pig distal colon. Am J Physiol 1990;258:G432–9.
  • Hemedah M, Loiacono R, Coupar IM, et al. Lack of evidence for histamine H3 receptor function in rat ileum and human colon. Naunyn Schmiedebergs Arch Pharmacol 2001;361:133–8.

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