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Selective expression of histamine receptors H1R, H2R and H4R, but not H3R, in the human intestinal tract

: Sander, L.E.; Lorentz, A.; Sellge, G.; Coeffier, M.; Neipp, M.; Veres, T.; Frieling, T.; Meier, P.N.; Manns, M.P.; Bischoff, S.C.


Gut 55 (2006), No.4, pp.498-504
ISSN: 0017-5749
Journal Article
Fraunhofer ITEM ()
enteric nervous system; histamine receptor; irritable bowel syndrome; inflammatory bowel disease; intestine; Food allergy

Histamine is known as a regulator of gastrointestinal (GI) functions such as gastric acid production, intestinal motility and mucosal ion secretion. Most of this knowledge was obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the GI tract is unclear. We therefore analysed HR expression in human GI tissue specimens by quantitative RT PCR and immunostaining and found that H1R, H2R and H4R mRNA were expressed throughout the GI tract, while H3R mRNA was absent. No significant differences in distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, rectum). Immunostaining of neurons and nerve fibres revealed that H3R is absent in the human enteric nervous system (ENS); 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 to controls. In conclusion, we demonstrate that H1R, H2R and, to some extent, H4R are expressed in the human GI tract, while H3R is absent, and we found that HR expression is altered in patients with GI diseases.