We are beginning to develop an understanding of the complex set of integrated signalling events that cooperate to limit the extent of epithelial chloride secretion in intestinal epithelial cells, details of which are provided in Figure 1. The significance of these findings lies in the knowledge that chloride secretion is demonstrably subject to inhibitory as well as stimulatory regulatory mechanisms, and the former might be exploited for antidiarrheal therapy. Likewise, growth factors and their receptors emerge as critical mediators of antisecretory signaling, and small molecule activators of consequent signals may be suitable as antidiarrheal drugs.
Figure 1) Signaling pathways shown to be involved in the negative regulation of calcium-dependent chloride secretion across intestinal epithelial cells. Epidermal growth factor (EGF) itself can reduce chloride secretion via effects on a basolateral potassium channel, as shown by the broken arrows. This pathway involves heterodimerization of the activated EGF receptor with another related family member, ErbB2. The acetylcholine analogue carbachol (CCh), on the other hand, acts initially to stimulate transient chloride secretion but subsequently trans-activates the EGF receptor via a signaling cascade that cleaves active transforming growth factor-alpha (TGFa) from a membrane-bound precursor. In an ErbB2-independent manner, the activated EGF receptors recruit extracellular signal-regulated protein kinase (ERK) isoforms of mitogen activated protein kinases that, via pathways that have yet to be fully elucidated, eventually block chloride secretion by interacting with a calcium-activated apical chloride channel (CLCA). Finally, growth hormone (GH) also appears to utilize the EGFr and ERK MAP kinases to reduce secretion. It likely does so by binding initially to its own receptor and subsequently recruiting effectors capable of EGF receptor transactivation (not shown here). Additional details are provided in the text. CaMK Calmodulin-activated protein kinase; InsP4 Inositol 3,4,5,6-tetrakisphosphate; PI3-K Phosphatidylinositol 3-kinase; PKC Protein kinase C All you need to discover how safe and advantageous it can be to purchase cialis super active online over the internet is visit the pharmacy suggested and enjoy your shopping experience as well as your treatment.