The secretory characteristics of dehydrocholate in the dog: comparison with the natural bile salts.

Abstract

During dehydrocholate administration in the taurine replete dog, the maximum excretory rate of total bile salt (almost entirely dehydrocholate derivative, mostly conjugated) was 3.84 .+-. 0.53 (SD) .mu.mol/min.cntdot.kg body wt (11 experiments). This was much less than the excretory maximum previously obtained for taurocholate (8.64 .+-. 1.31 (SD) .mu.mol/min.cntdot.kg) or actively conjugated cholate (6.83 .+-. 1.31 (SD) .mu.mol/min.cntdot.kg total cholate, mostly conjugated). The superimposition of taurocholate infusion did not cause any significant change in the dehydrocholate maximum but taurocholate itself was excreted into bile at no more than about half its normal maximum. When taurocholate maximum excretion was established 1st, it was reduced by dehydrocholate administration. In both types of experiment the joint bile salt excretory maximum was of the same order as that of taurocholate alone, provided taurocholate made up at least 40-50% of the total bile salt. When taurocholate administration was stopped, the maximum excretory rate of dehydrocholate rose to values up to 63% above the initially determined excretory maximum; the enhanced dehydrocholate excretory maximum, when calculated for optimal conditions, approached that of actively conjugated cholate, even though the effective dehydrocholate concentration in bile was 10-20.times. the critical micellar concentration of taurocholate. This suggests that the effective bile salt concentration in bile is not an important determinant of the secretory performance of a bile salt. It is necessary to postulate that taurocholate has both a facilitatory and an inhibitory action on dehydrocholate excretion. The facilitatory action, which persists after taurocholate has left the animal, may consist either of an increase in the maximum rate at which modification of dehydrocholate takes place within the liver cell, or an increase in the number of functioning carriers for dehydrocholate transfer. The inhibitory effect may be due to the competitive interaction that also appears to exist between the 2 bile salts. The increase in bile flow rate per unit increase in dehydrocholate excretion (15 ml/mmol) was about twice that obtained for taurocholate. There was no significant formation of micellar aggregates during dehydrocholate excretion, as judged from the total electrolyte concentration of bile and its osmolality. During the excretion of dehydrocholate-taurocholate mixtures (approximately 1:1) at submaximal rates the associated bile flow rate was not less than the sum of the separate components, suggesting that dehydrocholate was not being incorporated in taurocholate mixed micelles.