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Journal of Lipid Research, Vol. 24, 141-146, February 1983
Copyright © 1983 by Lipid Research, Inc.

Taurocholate is more potent than cholate in suppression of bile salt synthesis in the rat

J. M. Pries , A. Gustafson , D. Wiegand , and W. C. Duane

Departments of Medicine, Gastroenterology Sections, St. Paul Ramsey Medical Center, St. Paul, MN, and VA Medical Center and University of Minnesota, Minneapolis, MN

Synthesis of bile salts is regulated through negative feedback inhibition by bile salts returning to the liver. Individual bile salts have not been distinguished with regard to inhibitory potential. We assessed inhibition of bile salt synthesis by either cholate or its taurine conjugate in bile fistula rats. After allowing synthesis to maximize, baseline synthesis was determined by measuring bile salt output in four consecutive 6-hr periods. Next, sodium cholate (+[¹⁴C]cholate) or taurocholate (+[¹⁴C]taurocholate) was infused into the jugular vein for 36 hr and bile was collected in 6-hr aliquots. Hepatic flux of exogenous bile salt was determined by measuring output of radioactivity in bile divided by specific activity of the infusate. Synthesis was determined during the last four 6-hr periods of infusion by subtracting exogenous bile salt secretion from the total bile salt output. Thirteen studies using cholate and 13 using taurocholate were performed. Hepatic flux of infused bile salt varied from 1 to 12 µmol/100 g per rat per hr. Percent suppression of synthesis varied directly with hepatic flux of exogenous bile salt for both cholate and taurocholate in a linear fashion (r = 0.66, P < 0.01 and r = 0.87, P < 0.0005, respectively). Slope of the taurocholate line was 7.82 (% suppression/µmol per 100 g per hr), while slope of the cholate line was 3.66 (P < 0.05), indicating that taurocholate was approximately twice as potent as cholate in suppression of synthesis. At fluxes of 10-12 µmol/100 g per hr, taurocholate suppressed synthesis 84 ± 8 (SEM) % while cholate suppressed synthesis only 42 ± 12% (P < 0.02). The x-intercept of the taurocholate line was 0.65 (µmol/100 g per hr), while that of the cholate line was -1.01 (NS) suggesting that the threshold for initial suppression of synthesis did not differ for these two bile salts. We conclude that taurocholate is a more effective inhibitor of hepatic bile salt synthesis than cholate, and that intestinal deconjugation of bile salts may play a role in the regulation of synthesis.—Pries, J. M., A. Gustafson, D. Wiegand, and W. C. Duane. Taurocholate is more potent than cholate in suppression of bile salt synthesis in the rat.

Supplementary key words bile fistula rats

Submitted on May 27, 1981
Revised on October 13, 1982

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