Treatment of Crohn's disease（CD）and ulcerative colitis（UC）collectively known as inflammatory bowel diseases（IBD）has been a major clinical challenge whereas the incidence of IBD has been on the rise in ***（i...
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Treatment of Crohn's disease（CD）and ulcerative colitis（UC）collectively known as inflammatory bowel diseases（IBD）has been a major clinical challenge whereas the incidence of IBD has been on the rise in ***（ie 5-HT）released from enterochromaffin（EC）cells has recently been shown to promote mucosal immune and inflammatory *** I will present our recent experimental data that support the I channels（the hyperpolarisation-activated cyclic nucleotide-gated cation channels HCNs）as important regulators of EC cell function and *** of HCN2 in EC cells was confirmed by immunohistochemical staining of mouse rat and human gut *** the isolated mouse jejunum and colon adding exogenous cAMP（HCN2 activator）or cholera toxin（which increases endogenous cAMP）both caused an increase in 5-HT outflow which was blocked by ZD7288（HCN2 blocker）as well as mesenteric afferent nerve activity which was blocked by tropisetron（5-HT3R antagonist）.In DSS-induced murine IBD model in vitro colonic hypermotility and hypersensitivity were both attenuated by HCN2 blocker *** vivo preemptive and therapeutic administration of ivabradine ameliorated DSS-induced IBD-like disease activity and inflammatory injury of the colon and markedly decreased serum5-HT *** data raised the possibility of manipulating serotonin outflow to tame colonic inflammation and pain by blocking the Ichannels present on EC cells.
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