Alcoholism is the most frequent type of drug abuse and perhaps 10 million Americans can be classified as alcoholics. One of the complications frequently associated with chronic ingestion of alcohol is malnutrition and vitamin deficiency. While inadequate dietary intake may, at least in part, be responsible for this malnutrition the relative contribution of impaired intestinal absorption due to acute and/or chronic ingestion of alcohol remains the subject of controversy. The objective of the studies outlined in this proposal are to: 1) determine the effects of chronic ingestion of ethanol on """"""""active"""""""" transport of nutritionally and physiologically important compounds across the small intestine, 2) compare the absorptive responses of intestines from """"""""alcoholic"""""""" and normal animals to acute exposure to ethanol, 3) determine the effects of acute and chronic administration of ethanol on the """"""""active"""""""" transport systems localized in the brush border membranes of intestinal epithelial cells. For these purposes hamsters will be separated into two groups: an alcoholic group which will receive ethanol for 4 weeks and a pair-fed control group. Intestinal segments from alcoholics and controls will be mounted in Ussing chambers and the flux of 3-0-methyl glucose, L-alanine, folic acid and taurocholate across the segment will be measured in the absence and presence of ethanol. To insure that """"""""active"""""""" transport is being measured, the initial concentrations of the transported solute in the mucosal and serosal compartments will be the same. In addition, the permeability of the intestine will be determined by measuring serosal to mucosal fluxes of the above solutes when the solute is initially present only in the serosal compartment. In addition, brush border membrane viscles will be isolated from small intestines of alcoholic and pair-fed controls and used to determine the effects of acute and chronic ethanol exposure on: 1) the rate of uptake and maximum accumulation of D-glucose, L-alanine, folic acid and taurocholate, 2) the Km and Vmax for transport of the above solutes, 3) the rate of uptake of the above solutes in the absence of a driving force for accumulation (i.e. Na+ equilibrated across the brush border membrane) and 4) the rate of uptake of Na+. Finally, ileal enterocytes will be isolated from small intestines of alcoholic and control groups and used to determine the effect of acute and chronic ethanol exposure on binding of B-12 to the brush border and subsequent transfer from the brush border into the cell. The results of the above studies should provide considerable information regarding the effects of acute and chronic ethanol ingestion on intestinal absorption of solutes. That information should prove invaluable in developing treatments for alcoholics with absorptive deficits and for devising dietary regimens to provide adequate nutrition for abstinent alcoholics and for those continuing to ingest alcohol.
| Beesley, R C (1986) Ethanol inhibits Na+-gradient-dependent uptake of L-amino acids into intestinal brush border membrane vesicles. Dig Dis Sci 31:987-92 |
