The biological interactions between Pb and Ca are complex and not well- understoon, but can be demonstrated in virtually every tissue. High affinity lead-binding to intracellular calcium receptor and transport proteins as well as the involvement of lead in calcium-activated and calcium-regulating processes may provide a molecular basis for the broad spectrum cellar and systemic effects. The intestinal absorptive cells are responsible for transporting the entire body complement of calcium and most of the body lead burden. They represent, therefore, the first critical step in maintaining systemic and cellular homeostasis, as well as the first line of the defense against lead poisoning. Any interactions which occur at this level, either to enhance the body burden of Pb or to diminish the transport of calcium, may have serious health-related repercussions. The objectives of the proposed studies are; to detail those interactions involving calcium, lead, phosphorus and the vitamin D endocrine system which ultimately influence intestinal function and calcium homeostasis, and; to critically examine the intestinal transport pathways for calcium and lead. Experiments will be conducted to compare the effects of the vitamin D endocrine system on intestinal calcium and lead transport and body lead burden with special emphasis on lead intoxication. Similarly, the effects of dietary lead, calcium and phosphorus status and body lead burden on vitamin D endocrine system function will be examined. A whole animal model system will be employed. Intestinal lead and calcium absorption will be determined by the in situ ligated intestinal techniques. Direct intestinal interactions of lead and calcium will be investigated in addition to systemic interactions. The synthesis and circulating levels of 1,25(OH)2D as well as tibial and renal lead retention will be measured. These studies will be characterized by temporal comparisons of all variables and response elements to provide an integrated view of these complex interactions. Additional studies will focus on elucidating the intestinal transort pathways for lead and calcium as well as the possibility of interactions at specific sites. Ion microscopic and microautoradiographic techniques in combination with an in situ system will be employed to study integrated calcium and lead transport. Radiotracer uptake studies in microvillar and basolateral membrane vesicles will be used to examine specific transport events and the possibility of interactions.
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