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Gastrointestinal Histamine Receptor
Histamine occurs throughout the gastrointestinal tract, in enterochromaffin-like cells, restricted to the fundic mucosa of the stomach, mast cells and nerves. Histamine is actively produced and released in enterochromaffin-like (ECL) cells, rich in the synthesis enzyme, histidine decarboxylase (HDC), while it is mainly stored in mast cells.
Histamine exerts its effects through H1, H2, H3 and H4 receptors. Histamine H1 receptor are reported to be expressed on enterocytes, connective tissue cells, muscle layer, blood vessels, immune cells and ganglion cells of the myenteric plexus in the human intestine. H2 receptor appears to be located on parietal cells in the fundic mucosa and they have also been found in the intestinal epithelium, immune cells and myenteric ganglia in humans. The presence of H3 receptor in periphery remains controversial. H3 receptor mRNA expression is reported to be undetectable in peripheral tissues of humans and rats or alternatively to be restricted to liver and epithelia, including the mucosa of the gastrointestinal tract. H4 receptor mRNA appears to have a moderate to low expression in human stomach, small intestine and colon. Immunostaining revealed that enterocytes, intraepithelial neuroendocrine cells and leucocytes express the H4 receptor in human intestinal tissue. Histamine regulates multiple functions at the gastrointestinal level, contraction of intestinal smooth muscle is described as one of the best characterized responses mediated by H1 receptors. Throughout the gastrointestinal tract, contractile effects are also exerted on vascular smooth muscle and on endothelial cells, this latter resulting in an increase in vascular permeability. H2 receptors, located on parietal cells, are potent stimulants of gastric acid secretion, while the role of H3 and H4 receptors is less well defined. Nevertheless prevention of acute gastric injury, stimulation of mucus production and increase in gastric epithelial cell proliferation appear to be regulated by H3 receptors, but also in small intestine and colon, and the effect is selectively exerted on cells located in the proliferative compartments. H3 receptors also regulate neurotransmission in the myenteric plexus. Antagonists of H4 receptor have been recently shown to reduce tissue damage and inflammation in a rat model of colitis, suggesting a role of the receptor in gut inflammation. Is demonstrated that 50% of gastric mucosal histamine, in mice, derived from mast cells and that mast cell-derived histamine is not critical in the maintenance of gastric mucosal architecture. In addition, histamine and gastrin are mutually linked in the control of acid secretion while histamine and the H2 receptor do not exert a trophic effect and do not mediate the trophic action of gastrin.