Project: Research project

Grant Details


Rickets of prematurity is a common clinical entity occurring in 30 percent
of infants born weighing less than 2000 gm. The cause of this entity is
not known. Alteration in vitamin D metabolism and/or calcium and phosphate
intake or transport have all been propsed as etiological factors. Our lack
of understanding of this entity at least in part, stems from lack of basic
knowledge of intestinal transport of calcium (Ca) and phosphate (Pi) and
their relationship to vitamin D during early development. Because of the many functional similarities between the suckling rat
intestine and premature infant intestine, the principal investigator has
used suckling and weanling rats as models for studying the maturational
aspects of intestinal transport of minerals. Studies using in vivo
perfusion and in vitro everted gut sacs, suggested that intestinal Ca
transport shows a maturational phenomena with predominately passive process
in the suckling period which evolves to an active process by weaning. Recently, the use of isolated membrane vesicles from adult rat intestine
enabled an in-depth study of the transport of sugars and amino acids. We
have validataed the use of the membrane vesicles for the study of transport
during suckling and weanling periods in the rat. Using this methodology,
we propose a detailed examination of subcellular processes of Ca++ and Pi
transport during early life. The methods of procedure involve a sequential
breakdown of the small intestine from in vivo and in vitro experiments done
previously to progressively small functional components involved in
transcellular Ca++ and Pi transport. The proposal is designed to study: (1) The process by which Ca++ and Pi
enter into the intestinal epithelial brush border membrane; (2) The process
by which Ca++ and Pi exit at the basolateral membrane; (3) The role of 1-25
(OH)2 vitamin D3 in these two processes during early development. Since in
vivo studies suggested an important maturational effect, these processes
will be examined in an animal model during maturation (i.e., suckling and
weanling rats). The effects of vitamin D will be evaluated in offspring of
deficient mothers, vitamin D deficient rats treated with 1-25 (OH)2 D3 and
in vitamin D sufficient controls during the suckling and weanling periods;
and (4) Because the maturational changes in transport may be the results of
changes in membranes, the composition of brush border and basolateral
membranes in the suckling and weanling periods will be determined.
Effective start/end date12/1/8311/30/86


  • National Institutes of Health


  • Medicine(all)


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