Intestinal bile salt transport: structure-activity relationships and other properties

Abstract

Everted gut sacs of guinea pig intestine actively transport conjugated derivatives of cholanic acid having 2 or 3 hydroxyl groups or ketonic groups. The trihydroxy compounds are better transported than are the dihydroxy compounds. Among the dihydroxy compounds there was little difference in transport. The series of dihydroxy compounds included 2 unnatural compounds (7[alpha], 12[alpha] and 3-chloro, 7[alpha], 12[alpha]). The ability to be transported was not greatly influenced by changes in the conjugating moiety unless this involved changing the number of potential negative charges. A positively charged derivative was not transported. All active transport was limited to the ileum. The transport of a given bile salt is depressed in the presence of a 2nd. This is consistent with the operation of a single transport system; however, part of the mutual inhibition observed is attributable to a general effect of bile salts on mucosal function. Dihydroxy bile salts are more potent inhibitors than trihydroxy bile salts while the triketo derivative was the least potent.