Differing effects of hydroxy-7-oxotaurine-conjugated bile acids on bile flow and biliary lipid secretion in dogs

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Abstract
The effects on bile flow and biliary lipid secretion of 2 taurine-conjugated 7-oxo bile acids, 3.alpha.-hydroxy-7-oxo-cholanoyltaurine (I) and 3.alpha.,12.alpha.-dihydroxy-7-oxocholanoyl-taurine (II), were measured in the unanesthetized, chronic bile fistula dog. Each synthetically prepared compound, or cholyltaurine as control, was infused i.v. at a physiological rate of 1 .mu.mol .cntdot. kg-1 .cntdot. min-1 for randomized 90-min periods. Bile samples were collected and analyzed for biliary lipids (bile acids, phospholipid and cholesterol) and bile acid composition. Both compounds were secreted efficiently in bile, recovery averaging 90%. The trisubstituted compound (II) induced a greater choleresis and less phospholipid and cholesterol secretion than the disubstituted compound (I) or cholyltaurine. Each oxo compound was partially reduced during hepatic passage: about 47% of I (to mostly chenodeoxycholyltaurine) and about 30% of II (to mostly cholyltaurine). The effect of the individual bile acids on biliary lipid secretion was then calculated by assuming that the infused bile acid induced biliary lipid secretion after its hepatic biotransformation and each bile acid or its biotransformation product exerted an independent effect on biliary lipid secretion (expressed as a linkage coefficient, e.g., phospholipid secretion/bile acid secretion). For phospholipid, the calculated linkage coefficient for I was 0.31; for II, 0.07. For cholesterol, the calculated linkage coefficient for I was 0.014; for II, 0.003. In vitro studies indicated that the critical micellar concentration (CMC) in 0.15 M Na+ was 22 mM for I and 40 mM for II (compared with 6 mM for cholyltaurine). The disubstituted 7-oxo bile acid (I) has properties similar to those previously reported for chenodeoxycholyltaurine, whereas the trisubstituted 7-oxo compound (II) has properties quite different from those of cholyltaurine. Oxo bile acids with considerable higher CMC values than the common bile acids seem to induce more bile flow and less biliary lipid secretion.

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