RELATIVELY HIGH BILIARY SECRETORY MAXIMUM FOR NON-MICELLE-FORMING BILE ACID: POSSIBLE SIGNIFICANCE FOR MECHANISM OF SECRETION

¹ Department of Physiology, University of Liverpool, Liverpool, L69 3BX
² Department of Medicine, Division of Gastroenterology, University of California at San Diego, La Jolla, CA 92093, U.S.A.

Because of the formation of mixed micelles, the effective (i.e. monomeric, intermicellar) concentration of bile acid in bile is only a small fraction of the total concentration: this factor could be of critical importance for the net hepatic transport of the natural bile acids (especially transport across the canalicular membrane, which is hypothesized to be passive). To assess the influence of micelle formation on bile acid secretion, the rate-limiting canalicular transport of the natural, micelle-forming bile acid, cholyltaurine, was compared with that of the artificial non-micelle-forming bile acid, dehydrocholyltaurine (which undergoes partial reductive metabolism), in the anaesthetized rat with a bile fistula. The derivatives of dehydrocholyltaurine shared the same biliary transport system as cholyltaurine and had a secretory maximum ( 22 ± 4·7 (S.D.) µmol/min. kg, n = 12) which was significantly greater than that of cholyltaurine (15 ± 1·2, n = 6) (P 0·01). The biliary secretion rates of phospholipid and cholesterol during maximal secretion of dehydrocholyltaurine derivatives were not raised over control values; 3-hydroxy,7,12-dioxocholanoate (the taurine conjugate of which accounted for about 70-80% of the total bile acid in bile during dehydrocholyltaurine infusion) has also been shown in vitro to be non-micelle forming. These results would seem to indicate that micelle formation in bile is not essential for the effective net translocation of bile acid by the specific canalicular membrane carriers. The high maximal velocity with which dehydrocholyltaurine derivatives were secreted in the face of a bile acid activity in bile of one to two orders of magnitude greater than the intermicellar concentration of cholyltaurine suggests that an active transport system for bile acids may be located at the canalicular membrane.