DEVELOPMENT OF INTESTINAL ION TRANSPORT

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.