The purpose of the proposed research program is to gain an understanding of the mechanisms responsible for electrolyte transport by mammalian colon. Particular emphasis is placed on the effects of a variety of humoral, pharmacologic and pathologic agents on ion transport mechanisms of the colonic epithelium. This approach provides information on the nature of the transport processes and interactions among them. By employing both direct measurements of ion fluxes as well as electrophysiologic techniques, a complete analysis of transport mechanisms at the mucosal and basolateral membranes and movement through transepithelial paracellular pathways is obtained. An equivalent electrical circuit model for "sodium transporting" epithelia has been developed. This model will permit analysis of sodium transport across the mucosal and basolateral membranes in terms of equivalent electrical analogs (e.g. resistors and electromotive forces) and will assist in resolving the site(s) of action of various agents affecting Na absorption by the colon. In addition, the role of the sodium-potassium exchange pump in transepithelial sodium transport will be analyzed using a technique which permits direct measurement of potassium influx across the basolateral membranes from the serosal solution: The effects of agents which influence the rate of Na absorption will be investigated. BIBLIOGRAPHIC REFERENCES: Frizzell, R.A. and S.G. Schultz. Ion transport by rabbit colon: Effect of Amphotericin. Fed. Proc., in press, 1976. Frizzell, R.A., M.J. Koch and S.G. Schultz. Ion transport by rabbit colon I. Active and passive components. J. Membrane Biol. (in press) 1976.