Diarrheal disorders during the infancy period accounts for a significant percentage of morbidity and mortality. The reasons underlying such a high incidence of complications are not well known. Because the small intestine plays a major role in regulating ion transport, it is possible that the function of the small intestine during maturation in regard to ion transport may be different from the adult. The purpose of this proposal is to investigate in detail the maturational aspects of ion transport using brush border and basolateral membrane vesicles. Our laboratory has been actively engaged in the study of nutrient transport using membrane vesicles for the last several years. We have validated the use of brush border and basolateral membrane vesicles during maturation (suckling, weaning and adolescent rats). Our preliminary studies suggest the presence of Na+-H+ exchanger in the small intestine of rats during maturation. However the characteristics and the kinetics of this exchanger shows developmental pattern. We plan to use these established techniques to investigate further the process of Na+ and C1-entry and exit across brush border and basolateral membranes, respectively. In particular, the maturational aspects of Na+/H+ exchanger, Na+-C1- coupled transport and C1-HCO3-/or OH-exchanger at the brush border level and C1--HCO3-/or OH exchanger and the role of the two Na+ pumps at the basolateral membrane level will be investigated. Furthermore, we plan to probe the role of epidermal growth factor in modulating the process of Na+/H+ exchanger which has been shown to be the initiator for Na+ entry and subsequent alkalinization of the cell resulting in protein phosphorylation and DNA synthesis. The role of epidermal growth factor will be investigated in vivo in anew infant rat model in which rat pups are fed by orogastric tub an artifical foumula identical in composition to rat brest milk except for the absence of epidermal growth factor and in vitro by new system which involves preparing membrane vesicles from freshly prepared enterocytes primed with epidermal growth factor and agaents that modulate its effects.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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General Medicine A Subcommittee 2 (GMA)
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Vanderbilt University Medical Center
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United States
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Harrison, Christy A; Laubitz, Daniel; Ohland, Christina L et al. (2018) Microbial dysbiosis associated with impaired intestinal Na+/H+ exchange accelerates and exacerbates colitis in ex-germ free mice. Mucosal Immunol 11:1329-1341
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Ghishan, Fayez K; Kiela, Pawel R (2017) Vitamins and Minerals in Inflammatory Bowel Disease. Gastroenterol Clin North Am 46:797-808
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Johansson, Malin E V; Gustafsson, Jenny K; Holmén-Larsson, Jessica et al. (2014) Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut 63:281-91
Ghishan, Fayez K; Kiela, Pawel R (2014) Epithelial transport in inflammatory bowel diseases. Inflamm Bowel Dis 20:1099-109
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