The contribution of intestinal calcium transport to whole-body calcium homeostasis is well recognized but the details of the control of calcium absorption together with a quantitative appreciation for the role of regional calcium input through the intestine have not been clearly identified. Vitamin D stimulates intestinal calcium absorption but the relative roles of active and passive calcium fluxes in large and small intestine have received very little detailed attention. The role of the large intestine has been virtually ignored until very recently. Combining both biochemical and biophysical techniques to the study of intestinal calcium transport, it is hoped that the proposed research will identify the mechanisms responsible for transepithelial cellular calcium transport. The role of ion transport pumps at the level of the plasma membrane will focus a large fraction of the investigation. The interaction of these membrane-oriented pumps with vitamin D, regulatory ions such as calcium, and cytoplasmic regulators such as calmodulin and cyclic nucleotides will be studied in detail. Such investigations may increase our understanding of not only intestinal calcium transport but also the role of calcium in the control of absorption and secretion of electrolytes such as chloride and sodium together with associated water movements. Investigation of the cellular pathway for calcium absorption will be continued with in vitro rat large intestine (cecum). Investigation of the coupling of verapamilsensitive calcium entry at the apical cell pole with calcium efflux at the basolateral cell membrane via Ca-ATPase and Na:Ca exchange should provide increased understanding of intestinal calcium transport and its relation to cellular calcium homeostasis. The capacity to isolate specific transport components in the analysis of these problems represents a new and relative unexplored area of investigation for the intestine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036802-02
Application #
3235290
Study Section
General Medicine B Study Section (GMB)
Project Start
1985-12-01
Project End
1988-11-30
Budget Start
1986-12-01
Budget End
1988-11-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Favus, M J; Tembe, V (1992) The use of pharmacologic agents to study mechanisms of intestinal calcium transport. J Nutr 122:683-6
Favus, M J; Tembe, V; Ambrosic, K A et al. (1989) Effects of 1,25(OH)2D3 on enterocyte basolateral membrane Ca transport in rats. Am J Physiol 256:G613-7
Favus, M J; Mangelsdorf, D J; Tembe, V et al. (1988) Evidence for in vivo upregulation of the intestinal vitamin D receptor during dietary calcium restriction in the rat. J Clin Invest 82:218-24