The Regulation Mechanism Of Calcium Signaling In Intestinal Mucosal Epithelial Transport

Objective:?1?Previous studies are quite clear about the transport mechanism and molecular biology mechanism of intestinal messenger epithelium relying on cAMP,cGMP and other messenger cells.However,whether there exists the secretion mechanism of bicarbonate and chloride ion which depends on calcium signal alone,is unknown.In this study,the small intestine epithelium secretion relies on the secretion of bicarbonate and chloride ion regulated by calcium signal,we will opening up a new field for the regulation of calcium transport in intestinal epithelial cells.?2?It is well-known that the secretion of intestinal bicarbonate plays an important role in gut protection and body acid-base balance.The secretion of chloride is closely related to intestinal water secretion,diarrhea and constipation.Through the calcium-mediated intestinal Mucosal epithelial transport regulation mechanism can play critic role in the protection of intestinal barrier and regulation of intestinal water secretion,and provides a new potential drug targets for the ulcer,inflammatory bowel disease?IBD?,diarrhea,constipation and other diseases;Methods:Ussing Chamber?Multi-channel current clamp?is a tool for studying trans-epithelial transport,which can be used for research ion transport,nutrient transport and drug transport.We took the mouse duodenal epithelium,used Ussing Chamber instrument examine the short-circuit current?Isc?changes after different experimental reagents which activated apical membrane and basolateral membrane in duodenum epithelial cells.Response to different polarity of the duodenal epithelium-related protein expression and biological function of the ion channel.Results:Caffeine activates the RyR receptor on the endoplasmic reticulum/sarcoplasmic reticulum,which was significantly inhibited in Ca²⁺-free serosal solution and by several selective store-operated Ca²⁺channels?SOC?blockers added to the basolateral membrane of duodenal tissues.Furthermore,we found that CRAC/Orai channels may represent the molecular candidate of SOC in intestinal epithelium.The increase of intracellular calcium and the extracellular calcium entry together lead to CaCCs and AE on the apical membrane side of duodenal epithelium.The short-circuit current can be inhibited by inhibitors of CaCCs and AE.In addition,we found that cAMP pathway agonists can enhance the short circuit caused by caffeine action Current,the two together and before and after the addition of the intensity of the enhanced current are somewhat different.Conclusion:Ca²⁺signaling plays a critical role in intestinal ion secretion via CRAC/Orai-mediated SOCE mechanism on the serosal side of epithelium.We also demonstrated the molecular mechanisms of Ca²⁺signaling in CaCCs and AE-mediated secretion.The classical cAMP pathway,is involved in this Caffein-induced Ca²⁺-meditation secretion,to regulate and promote the role of secretion.Our findings provide new drug targets for protecting the upper gastrointestinal mucosa and maintaining the water-electrolyte balance in the small intestine.