Neuropeptide receptor expression in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD), i.e. Crohn__s disease and ulcerative colitis are characterized by a chronic inflammation of the gastrointestinal tract. Neuropeptides are involved in the regulation of intestinal motility, chloride secretion and inflammatory response, three processes that are disturbed in patients with IBD. This has led to the suggestion that neuropeptides are involved in the pathology of IBD. Neuropeptides exert their effects by binding to specific cell surface receptors, a better understanding of these receptor expression patterns in normal and diseased intestine may lead to new diagnostic and therapeutic approaches. In this thesis the receptor expression of the neuropeptides substance P, neurotensin, gastrin-releasing peptide and motilin was studied. In IBD patients, an increased mucosal substance P receptor expression and a decreased muscular neurotensin receptor-1 and -3 expression was found. No neurotensin receptor-2 was detected in the human intestine. The expression of the gastrin-releasing peptide receptor in the smooth muscle was decreased in Crohn__s disease and not in ulcerative colitis. For the first time motilin receptor expression was demonstrated in human intestinal mucosa, but no differences were observed between IBD and controls. Overall this thesis contributes to a better understanding of neuropeptide receptor expression in control and IBD human tissue.