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  • Title: Effect of cholylsarcosine on hepatic cholesterol and bile acid synthesis and bile secretion in rats.
    Author: Heuman DM, Vlahcevic ZR, Pandak WM, Hylemon PB, Kim YS, Lillienau J, Hofmann AF.
    Journal: Gastroenterology; 1992 Nov; 103(5):1641-8. PubMed ID: 1385253.
    Abstract:
    The regulatory and secretory properties of cholylsarcosine (C-sar), a synthetic conjugated bile acid analogue that resists deconjugation and dehydroxylation, were compared with those of the natural conjugates of cholic acid. After continuous intraduodenal infusion of cholylsarcosine (C-sar), cholyltaurine (C-tau), or cholylglycine (C-gly) at 36 mumol/100 g.h, the infused bile acid in each case became the predominant biliary bile acid. After 48 hours, infusion of C-sar, C-tau, and C-gly suppressed the activity of cholesterol 7 alpha-hydroxylase (C7 alpha H; rate-limiting for bile acid synthesis) by 65%, 78%, and 92%, respectively, compared with biliary fistula controls. After C-sar infusion, levels of C7 alpha H protein, messenger RNA, and transcriptional activity were depressed to the same extent as specific activity, indicating that C-sar, like C-tau, down-regulates C7 alpha H principally at the level of gene transcription. All three bile acids also suppressed activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (rate-limiting for cholesterol synthesis). Both short- and long-term, the three cholyl conjugates caused similar increases in bile flow and in biliary secretion of cholesterol and phospholipid. It is concluded that in the rat, cholyl conjugates per se can suppress cholesterol and bile acid biosynthesis without prior conversion to deoxycholate. The effects of C-sar on hepatic cholesterol and bile acid synthesis as well as on induced bile flow and biliary lipid secretion are essentially identical to those of the naturally occurring cholyl conjugates.
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