The mechanisms for initiating the transition from fluid secretion by fetal lungs to fluid absorption by neonatal lungs are unknown. The long term objective of the research is to compare the apical and basolateral transport processes of fetal and postnatal lung epithelium so that models of transition form C1-dependent secretion to Na+-dependent absorption may be tested. The immediate objectives of this proposal are to prepare apical and basolateral vesicles from adult type II alveolar cells and to examine hypothesized transport processes with radioisotopes, ion-specific electrodes, and ion-specific dyes. Specifically, the aims are to prepare and isolate apical and basolateral plasma membrane vesicles form adult rat type II alveolar cells; investigate apical Na+ and C1- electrogenic conductances; investigate basolateral Na+/C1- and Na+/Ca++ transport processes examine modulatory effects of Ca++ and c-AMP on transport processes; and initiate studies of membrane conductance employing planar phospholipid bilayers which require very small quantities of membrane and are preparatory to future studies involving limited quantities of fetal tissue. Data derived from these studies will permit hypothesis-testing of secretory and absorptive mechanisms including the suggestion that the perinatal transition from these studies will permit hypothesis-testing of secretory and absorptive mechanisms including the suggestion tat the perinatal transition from apical C1- secretion to Na+ absorption develops with the appearance of basolateral C1- conductance. The environment in which the project will be conducted is ideal for the investigation of epithelial transport processes. In addition to the sponsor who is an international authority on the preparation of and transport by upper airway vesicles, the local faculty includes many prominent investigators of epithelial membrane transport. In summary, study of ion transport by apical and basolateral vesicles of type II alveolar cells will yield information, which is currently unavailable by conventional electrophysiologic and radioisotope techniques. Moreover, increased understanding of pulmonary disorders involving lung fluid imbalance during and beyond the perinatal period is anticipated which will contribute to better therapeutic modalities.
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|Oelberg, D G; Xu, F (1998) Conductive choline transport by alveolar epithelial plasma membrane vesicles. Mol Genet Metab 65:220-8|
|Shabarek, F; Xu, F; Oelberg, D G (1994) Sodium chloride cotransport at the basolateral membrane of type II pneumocytes. Biochem Med Metab Biol 52:76-83|
|Oelberg, D G; Xu, F; Shabarek, F (1994) Sodium-coupled transport of glucose by plasma membranes of type II pneumocytes. Biochim Biophys Acta 1194:92-8|
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