BINDING OF BILE-ACIDS WITH RAT COLON AND RESULTANT PERTURBATION OF MEMBRANE ORGANIZATION AS STUDIED BY UPTAKE MEASUREMENT AND P-31 NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY

Abstract

The mode of interaction of deoxycholate (DOC) or lithocholate (LC) and F344 rat colon was examined by measurements of uptake, 31P NMR spectroscopy and observation of morphological changes. DOC as well as LC was taken up by the colon in a nonsaturable manner with respect to concentration and time, up to 30 min. None of several metabolic inhibitors reduced the uptake of the bile acids, nor did pretreatment of colon segments with chloroform-methanol (2:1, (vol/vol)), heat or trypsin. Further, the bile acids were not transported by the colon against concentration gradients, and they were bound to both the mucosa and serosa equally. The bile acids are transported in a passive manner, and no specific receptor for them is contained in colonic mucosa. The uptake of the bile acids by the colon varied with temperature and was related to the fluidity of the colonic membranes. The extent of uptake of hydrocholate and taurocholate, which do not induce ornithine decarboxylase (ODC) activity, was almost the same as that of LC. The 31P NMR spectra of the colonic mucosal cells indicated that the proportion of the bilayer structure is increased by 0.5mM DOC. Among a variety of bile acids examined, the extent of membrane alteration was in parallel with the extent of ODC induction. Treatment of the colonic mucosa with 0.5mM DOC caused marked degeneration of the surface but not the deeper layers of the mucosa. Thus, physiological concentrations of bile acids influence the membrane organization of the colonic mucosa in a nonspecific manner that is possibly related to the tumor-promoting activity.