Effects of sulfation patterns on intestinal transport of bile salt sulfate esters.

The absorption of 14C-labeled 3 alpha-, the 7 alpha- and the 3 alpha,7 alpha-sulfate esters of taurochenodeoxycholate by guinea pig small intestine was studied using in vivo and in vitro preparations. In vivo ileal perfusions showed that sulfation markedly decreased uptake by the ileal bile salt transport system and that the position and number of the sulfate radicals affected the degree of transport inhibition. The following relationships were found: transport of taurochenodeoxycholate (TCDC) greater than TCDC-3-sulfate greater than TCDC-7 sulfate greater than TCDC-3,7-disulfate with a decrease of approximately 90% between each pair. In vitro, jejunal perfusions demonstrated that sulfation also decreased passive flux. By use of an everted gut sac technique, the ability of ileum to move the sulfated bile salts against a concentration gradient was measured. Under these conditions transport of TCDC-3-sulfate was minimal, and that of the 7-sulfate and 3,7-disulfate was not observed. In view of the reported increased levels of sulfated bile salts after total or partial biliary tract obstruction, our results support the concept of sulfation as an adaptive mechanism for enhancing fecal elimination of bile salts.