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  • Title: Effect of a new synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on cholesterol synthesis and low density lipoprotein uptake by primary cultures of rat hepatocytes.
    Author: Saito Y, Shiki Y, Shirai K, Yoshida S.
    Journal: Arzneimittelforschung; 1988 Feb; 38(2):251-3. PubMed ID: 3130840.
    Abstract:
    CS-514 ((+)-sodium (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methyl-butyryl]-1,2,6,7,8-hexahydro-1-naphthyl] heptanoate) which was recently synthesized as an inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase lowers serum cholesterol levels. This compound inhibited cholesterol synthesis dose-dependently from acetate in primary cultures of rat hepatocytes. At high concentration (0.5 and 5.0 mumol/l), but not at lower concentration, it inhibited bile formation from acetate. Low density lipoprotein (LDL)-[3H]-cholesteryl linoleate incorporation into hepatocytes was increased when the cells were preincubated with 0.5 or 5.0 mumol/l CS-514 for 12 h. Bile formation from LDL-[3H]-cholesterol linoleate was not affected by addition of CS-514. These results suggest that inhibition of de novo cholesterol synthesis by CS-514 enhanced LDL receptor function in primary cultures of rat hepatocytes and lowered LDL-cholesterol level.
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