How can we battle the scourge of diarrhea: EPITHELIAL SECRETORY FUNCTION (Part 2)

EGF receptors and relevant ligandsMoreover, because EGF receptors and relevant ligands (including EGF itself and transforming growth factor-alpha [TGFa]) may be regulated in the setting of intestinal injury and inflammation, the beneficial effects of EGF on net fluid transport may represent an adaptive response that protects the body from excessive fluid loss . We have shown that EGF inhibits chloride secretion via an intracellular signaling pathway that sequentially recruits the enzymes phosphatidylinositol 3-kinase and protein kinase C to the basolateral membrane of secretory epithelial cells, ultimately limiting chloride secretion by reducing the activity of a baso-lateral potassium channel . If potassium cannot be recycled across this membrane, the driving force for chloride exit through apical chloride channels is lost.

We have also identified a possible role for the EGF receptor in accounting for the transient nature of secretion evoked by calcium-dependent chloride secretagogues, such as acetylcholine. Thus, cholinergic agonists appear to activate an autocrine signaling loop that results in the release of TGFa from intestinal epithelial cells, in turn resulting in activation of the EGF receptor and recruitment of downstream kinases, such as the extracellular signal-regulated protein kinase (ERK), isoforms of mitogen activated protein (MAP) kinases. These also seem capable of inhibiting secretion, albeit via mechanisms and targets that have yet to be defined. In a similar vein, growth hormone, a major mediator of somatic cell growth and a possible therapy for diarrhea and tissue injury in Crohn’s disease, is also capable of limiting epithelial chloride secretion via a mechanism that involves the EGF receptor and ERK MAP kinases. Find out more about your chance to visit the most trusted pharmacy you could ever find to get cialis super active online pharmacy in the amounts required, without any need to see your health care provider first or get a prescription.

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