Our recent studies have delineated the distinct transport parameters of rabbit proximal colon in vitro. This research proposal focuses on the relationship of these in vitro transport parameters to the biological functions of the proximal colon, primarily the regulation of Na absorption and the disposition of short-chain fatty acids. The principal ion transport mechanism in proximal colon is Na+H exchange. We have identified several stimuli for this absorptive process including epinephrine, glucocorticoids, proprionate, removal of HCO3 and lowered [Na] in the in vitro bathing media. Both amiloride and cyclic AMP inhibit this transport under various conditions. We have demonstrated amiloride-inhibitible hydrogen ion secretion in the proximal colon. The studies in this grant are designed to investigate the mechanism of Na absorption, its regulation, and the interaction of agents that increase and decrease ion transport. To study this process we will use Ussing chambers to measure transepithelial transport; a pH stat system to determine hydrogen ion secretion; conventional micro-electrodes to determine intracellular potential difference and ionic conductances of the apical and basolateral membranes; and pH-selective microelectrodes to measure changes in intracellular pH. The predominant luminal anions in the proximal colon are short-chain fatty acids. Their role in ion transport in vitro has yet to be clearly defined; however, their relation to Na transport and potential role as a significant source for calories (""""""""colonic salvage"""""""") are major factors in the function of the proximal colon as a discrete segment of the gastrointestinal tract. We will study short-chain fatty acid transport in vitro to determine whether active transport is present, the relationship to Na absorption and whether the acid or ionized form is the predominant species transported. Na-H exchangers are found in a wide variety of transport epithelia and are of generalized physiologic interest. Na-H exchange in proximal colon exhibits unique regulatory features that make its study particularly relevant for understanding Na absorption in this part of the gut. By characterizing the specific transport processes of proximal colon, we will achieve a better understanding of the nature of the segmental heterogeneity of the gut and will gain insight into the gut's handling of fluid and electrolytes, the pathophysiology of diarrhea and the possible role of the colon as a nutritive organ.
