STUDIES ON THE MECHANISM OF INTESTINAL PASSAGE OF THE FOOD COMUTAGEN HARMAN, IN THE RABBIT

The passage of harman (Ha) across rabbit jejunum and its effects on electrical parameters of the intestinal epithelium were studied in vitro using Ussing chambers. A linear relationship between mucosal to serosal flux (J(m-s)) and the concentration of Ha (0.25-2mM) was found. Ha elicited a dose-related decrease in short-circuit current, but did not affect transmural potential difference. At 2 mM, Ha decreased tissue conductance. Despite changes of electrical parameters, J(m-s) of Ha was not modified by metabolic effecters such as glucose, colchicine, 2,4-dinitrophenol and ouabain, indicating that passage was dependent neither on membrane movements nor on cell energy. The transport of Ha was not dependent on Na+, but Ha inhibited in a dose-related manner the cotransport of Na+ and glucose. Luminal sodium taurocholate or beta-lactoglobulin had no appreciable effect on transport of Ha, but ethanol elicited a 45%,increase in Ha permeability. These results indicate (1) that substantial amounts of Ha can cross the intestinal epithelium by the transcellular pathway and (2) that the passage of Ha, which appears to be diffusional, is not affected by luminal solutes such as glucose, sodium taurocholate and beta-lactoglobulin, but is markedly enhanced by ethanol.