The biological interactions between lead and calcium are complex and little is currently known regarding the cellular and molecular nature of these interactions. The intestinal epithelial absorptive cells are responsible for transporting the entire body complement of calcium and most of the body burden of lead. They represent, therefore, the first critical step in maintaining systemic and cellular calcium homeostasis as well as the first line of defense against lead poisoning. Any interactions which occur at this level, either to enhance the body burden of lead or to diminish the transport of calcium, may have serious health-related repercussions. The objectives of the proposed studies are to define the interactions which occur between lead and calcium at the level of the intestinal cell and to determine the mechanisms whereby these interactions affect the intestinal transport of both lead and calcium. Emphasis will be placed on comparing and contrasting the behavior of lead and calcium in response to a number of experimental conditions. Experiments will be conducted to examine the possibility that lead and calcium share a common transport system, or individual components of such a system. In situ ligated intestinal loops from chicks will be employed to study the effects of dietary calcium and vitamin D status on the intestinal transport of lead. Specific attention will be given to identifying any direct interactions, in vivo, between lead and calcium which alter the absorption of either element. Additional studies will focus on the extent and nature of the observed inhibition of vitamin D-mediated intestinal calcium transport by dietary lead intoxication. The effect of lead intoxication on lead transport will also be studied. Specific aspects to be examined with regard to lead toxicity are: 1) the localization of the hormonal form of vitamin D in the intestinal tissue; 2) the involvement of intestinal protein synthesis; 3) the entry of calcium (and lead) into the cell across the brush border membrane; 4) the transfer of calcium and lead through the cytosol, and; 5) the extrusion of calcium and lead from the cell across the basal-lateral membranes. These studies will employ both in vivo techniques and in vitro membrane vesicle preparations. The localization of lead within the intestinal tissue will also be examined under a variety of experimental conditions by ion microscopy.
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