Identification of histamine receptors in the canine gastrointestinal tract

The important role of histamine in chronic gastrointestinal diseases has been increasingly recognized over the last two decades in human medicine. Histamine is released following mast cell activation and exerts its action through binding to four different histamine receptors (H1, H2, H3, and H4). Histamine receptors are dispersed throughout the body, and each different receptor mediates a unique response. Documentation of the presence and type of histamine receptors in the differing sections of the canine gastrointestinal tract will provide additional research opportunities to further explore the role of histamine and its receptors in chronic canine enteropathies, as well as potential therapeutic options. Full thickness gastric, duodenal, jejunal, ileal, and colonic biopsies were obtained from 6 clinically normal adult dogs immediately after humane euthanasia. Commercially available histamine receptor antibodies predicted to react with canine tissues were applied to paraffin-embedded tissue sections using standard immunohistochemistry techniques to identify different histamine receptors. Staining intensity was graded from negative to strong, and the specificity of each antibody was evaluated with western blot. The presence and distribution of histamine receptors varied by anatomic site and histologic level within sections of the canine gastrointestinal tract. All 4 histamine receptors were readily identified, although the distribution of H4 receptors was decreased in comparison to the other histamine receptors. The distribution of the various histamine receptors was similar to that seen in the normal human gastrointestinal tract. H1 receptors were located in the stomach, lymphoid tissue of the ileum and colon, and the smooth muscle and ganglia of all sections. H2 receptors were located in all sections of the gastrointestinal tract, with greatest staining intensity in the gastric mucosa. H3 receptors were located in the stomach and colonic mucosa, smooth muscle and ganglia of all sections, and ileal and colonic lymphoid tissue. H4 receptors were located in the ganglia and smooth muscle of the gastrointestinal tract, as well as the gastric and colonic mucosal and ileal lymphoid tissue. Western blot demonstrated both specific and non-specific staining with the H1 and H3 receptor antibody, but good specificity with the H4 receptor antibody. The H2 receptor antibody was not compatible with western blot techniques, despite excellent immunohistochemical specificity and consistency. Further studies to compare the density and distribution of the various histamine receptors in dogs with gastrointestinal disease are warranted.