Chapter 65 - Water Transport in the Gastrointestinal Tract

Abstract

Abstract Large quantities of fluid are transported across epithelial barriers in the gastrointestinal (GI) tract for secretion of saliva, gastric juice, bile and pancreatic fluid, and for fluid absorption in the intestine. The molecular pathways for water transport in the GI tract have been identified relatively recently and remain an evolving and in some cases controversial subject. As in other organ systems, the general paradigm in the GI tract is that water movement occurs secondary to osmotic driving forces created by active salt transport and to hydrostatic pressure differences. This chapter describes current concepts in fluid transporting mechanisms, from the original standing-gradient model to newer speculative models involving water pumps, electroosmosis, and osmosensing feedback. This chapter also describes potential roles for aquaporin (AQP) water channels in GI fluid transport. The AQPs are a family of small, integral membrane proteins that transport water and in some cases water and small solutes such as glycerol and hydrogen peroxide. AQPs are expressed widely in cell plasma membranes in epithelial, endothelial, and other cell types in the GI tract and elsewhere, including in salivary gland, liver, pancreas, gallbladder, and intestine. There is compelling evidence for the physiological importance of some AQPs in some tissues based on studies in humans with AQP deficiency/mutations, and phenotype analysis of transgenic mouse models of AQP deletion. In the GI tract, there is good evidence for the involvement of AQPs in salivary gland secretion and intestinal epithelial repair, though little evidence for other proposed functions such as intestinal fluid transport, and bile and pancreatic fluid secretion. AQPs are strongly expressed in GI tumors, though their role in tumor growth and spread remains unproven. Finally, the potential utility of AQP-targeted therapeutics, such as gene delivery and small molecule AQP-modulating drugs, is discussed.