These investigations are directed toward increasing our knowledge of the regulation of Na and Cl transport in the rat colon. The mammalian large intestine is critically important in the pathogenesis of diarrhea since alterations of colonic fluid absorption and the colonic absorptive capacity are primary determinants of the genesis of diarrhea regardless of the primary site of altered fluid and electrolyte transport. These studies will continue investigations of electrolyte transport using isolated intact epithelium and will study both basal Na and Cl transport as well as the mechanism by which agents that increase and decrease electrolyte Na and Cl absorption. Major emphasis will be directed toward clarifying the nature of neutral NaCl absorption which in this epithelia is the mechanism largely responsible for Na and Cl absorption. In addition, the K dependency of Na and Cl absorptive and secretory processes will be determined. The mechanism by which angiotensin and enkephalin increase colonic Na and Cl movement will be studied as well as the role of substance P in the regulation of Cl secretion. In other experiments, studies will be initiated to establish methods to isolate apical and basolateral membrane vesicles of colonic epithelium. With the availability of such vesicles, attention will be directed toward determining whether neutral NaCl absorption observed in intact tissue represents coupled NaCl cotransport or dual ion exhanges (Na/H and Cl/HCO3 or Cl/OH).
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