Intestinal Membrane Structure and Functional Development

Schwarz, Steven

Abstract

The research proposed in this application is based upon the large body of evidence demonstrating that both structural and functional characteristics of the small intestinal epithelial cell microvillus membrane (MVM) in the rat, undergo significant change during early postnatal development and during periods of altered nutrition. The central focus of these studies will be to investigate lipid-dependent (i.e. intrinsic) properties of the MVM, in contrast to well described lipid-independent (i.e. extrinsic) characteristics. Initial experiments will confirm the observations that MVM lipid compositon undergoes marked developmental change, determine the extent of change and document variation in major lipid moieties (cholesterol, phospholipid, fatty acid), utilizing thin layer an gas-liquid chromatographic techniques. The influence of these changes on physical-chemical properties of MVM lipid will be evaluated, utilizing estimates of membrane fluidity derived by fluorescence polarization spectrometry, nd Arrhenius plots of intrinsic intestinal hydrolase activities. Subsequent studies will provide a developmental analysis of solute transport (D-glucose, bile salt) in isolated MVM vesicles, and correlate maturation of these properties with the observed structural and physical-chemical changes. Studies will also be carried out in animals subjected to early postnatal under- and overnutrition and premature weaning to determine the effects during development of altered nutritional homeostasis on MVM intrinsic structural-functional characteristics. In older animals, effects on lipid-dependent properties of the mature MVM resulting from altered nutrition will be determined. Experiments during total parenteral nutrition will determine the requirement for enteral nutrition per se, and effects on the MVM of essential fatty acid deficiency will be studied. Finally, studies in animals subjected to duodenoileal bypass will determine the role of gestational secretions in maintenance of MVM structure and function. The entire project will provide valuable information concerning the developmental and nutritional determinants of intestinal microvillus membrane structure and function; and these studies may offer a basis for understanding more completely, in the human, observed effects during defined clinical situations.